Method and apparatus for three-dimensional fabrication with feed through carrier

ABSTRACT

A method of forming a three-dimensional object, is carried out by (a) providing a carrier and a build plate, the build plate comprising a semipermeable member, the semipermeable member comprising a build surface with the build surface and the carrier defining a build region therebetween, and with the build surface in fluid communication by way of the semipermeable member with a source of polymerization inhibitor; (b) filling the build region with a polymerizable liquid, the polymerizable liquid contacting the build surface; (c) irradiating the build region through the build plate to produce a solid polymerized region in the build region, while forming or maintaining a liquid film release layer comprised of the polymerizable liquid formed between the solid polymerized region and the build surface, the polymerization of which liquid film is inhibited by the polymerization inhibitor; and (d) advancing the carrier with the polymerized region adhered thereto away from the build surface on the build plate to create a subsequent build region between the polymerized region and the build surface; (e) wherein the carrier has at least one channel formed therein, and the filling step is carried out by passing or forcing the polymerizable liquid into the build region through the at least one channel. Apparatus for carrying out the method is also described.

RELATED APPLICATIONS

This application is a continuation of PCT Application No.PCT/US2014/015497, filed Feb. 10, 2014, which in turn claims the benefitof commonly owned U.S. Provisional Patent Application Ser. No.61/919,903, filed Dec. 23, 2013; 61/865,841, filed Aug. 14, 2013 and61/763,746, filed Feb. 12, 2013, the disclosures of which areincorporated by reference herein in their entirety.

FIELD OF THE INVENTION

The present invention concerns methods and apparatus for the fabricationof solid three-dimensional objects from liquid polymerizable materials.

BACKGROUND OF THE INVENTION

In conventional additive or three-dimensional fabrication techniques,construction of a three-dimensional object is performed in a step-wiseor layer-by-layer manner. In particular, layer formation is performedthrough solidification of photo curable resin under the action ofvisible or UV light irradiation. Two techniques are known: one in whichnew layers are formed at the top surface of the growing object; theother in which new layers are formed at the bottom surface of thegrowing object.

If new layers are formed at the top surface of the growing object, thenafter each irradiation step the object under construction is loweredinto the resin “pool,” a new layer of resin is coated on top, and a newirradiation step takes place. An early example of such a technique isgiven in Hull, U.S. Pat. No. 5,236,637, at FIG. 3. A disadvantage ofsuch “top down” techniques is the need to submerge the growing object ina (potentially deep) pool of liquid resin and reconstitute a preciseoverlayer of liquid resin.

If new layers are formed at the bottom of the growing object, then aftereach irradiation step the object under construction must be separatedfrom the bottom plate in the fabrication well. An early example of sucha technique is given in Hull, U.S. Pat. No. 5,236,637, at FIG. 4. Whilesuch “bottom up” techniques hold the potential to eliminate the need fora deep well in which the object is submerged by instead lifting theobject out of a relatively shallow well or pool, a problem with such“bottom up” fabrication techniques, as commercially implemented, is thatextreme care must be taken, and additional mechanical elements employed,when separating the solidified layer from the bottom plate due tophysical and chemical interactions therebetween. For example, in U.S.Pat. No. 7,438,846, an elastic separation layer is used to achieve“non-destructive” separation of solidified material at the bottomconstruction plane. Other approaches, such as the B9Creator™3-dimensional printer marketed by B9Creations of Deadwood, S. Dak., USA,employ a sliding build plate. See, e.g., M. Joyce, US Patent App.2013/0292862 and Y. Chen et al., US Patent App. 2013/0295212 (both Nov.7, 2013); see also Y. Pan et al., J. Manufacturing Sci. and Eng. 134,051011-1 (October 2012). Such approaches introduce a mechanical stepthat may complicate the apparatus, slow the method, and/or potentiallydistort the end product.

Continuous processes for producing a three-dimensional object aresuggested at some length with respect to “top down” techniques in U.S.Pat. No. 7,892,474, but this reference does not explain how they may beimplemented in “bottom up” systems in a manner non-destructive to thearticle being produced. Accordingly, there is a need for alternatemethods and apparatus for three-dimensional fabrication that can obviatethe need for mechanical separation steps in “bottom-up” fabrication.

SUMMARY OF THE INVENTION

Described herein are methods, systems and apparatus (includingassociated control methods, systems and apparatus), for the generallycontinuous production of a three-dimensional object. In these methods,systems and apparatus, the three-dimensional object is produced from aliquid interface. Hence they are sometimes referred to, for convenienceand not for purposes of limitation, as “continuous liquid interphaseprinting.” A schematic representation is given in FIG. 1 herein.

As discussed below, the interface is between first and second layers orzones of the same polymerizable liquid. The first layer or zone(sometimes also referred to as a “dead zone”) contains an inhibitor ofpolymerization (at least in a polymerization-inhibiting amount); in thesecond layer or zone the inhibitor has been consumed (or has nototherwise been incorporated or penetrated therein) to the point wherepolymerization is no longer substantially inhibited. The first andsecond zones do not form a strict interface between one another butrather there is a gradient of composition that can also be described asforming an interphase between them as opposed to a sharp interface, asthe phases are miscible with one another, and further create a(partially or fully overlapping) gradient of polymerization therebetween(and also between the three-dimensional object being fabricated, and thebuild surface through which the polymerizable liquid is irradiated). Thethree-dimensional object can be fabricated, grown or producedcontinuously from that gradient of polymerization (rather thanfabricated layer-by-layer). As a result, the creation of fault orcleavage lines in the object being produced, which may occur inlayer-by-layer techniques such as described in Y. Pan et al. or J. Joyceet al. (noted above), may be reduced or obviated. Of course, such faultor cleavage lines can be intentionally introduced when desired asdiscussed further below.

In some embodiments of continuous liquid interphase printing, the firstlayer or zone is provided immediately on top of, or in contact with, abuild plate. The build plate is transparent to the irradiation whichinitiates the polymerization (e.g., patterned radiation), but the buildplate is preferably semipermeable to the polymerization inhibitor andallows the inhibitor of polymerization (e.g., oxygen) to pass partly orfully therethrough (e.g., to continuously feed inhibitor to the “deadzone”). The build plate is preferably “fixed” or “stationary” in thesense that it need not slide, retract, rebound or the like to createseparate or sequential steps (as in a layer-by layer process). Ofcourse, minor motion of the build plate in the x and/or y directionsthat does not unduly disrupt the gradient of polymerization, but stillpermits continuous polymerization from the liquid interface, may stillbe accommodated in some embodiments, as also discussed below.

Thus the present invention provides a method of forming athree-dimensional object, comprising: providing a carrier and anoptically transparent member having a build surface, said carrier andsaid build surface defining a build region therebetween; filling saidbuild region with a polymerizable liquid; irradiating said build regionthrough said optically transparent member to form a solid polymer fromsaid polymerizable liquid while concurrently advancing said carrier awayfrom said build surface to form said three-dimensional object from saidsolid polymer, while also concurrently (i) continuously maintaining adead zone of polymerizable liquid in contact with said build surface,and (ii) continuously maintaining a gradient of polymerization zonebetween said dead zone and said solid polymer and in contact with eachthereof, said gradient of polymerization zone comprising saidpolymerizable liquid in partially cured form (e.g., so that theformation of fault or cleavage lines between layers of solid polymer insaid three-dimensional object is reduced). In some embodiments, theoptically transparent member comprises a semipermeable member, and saidcontinuously maintaining a dead zone is carried out by feeding aninhibitor of polymerization through said optically transparent member,thereby creating a gradient of inhibitor in said dead zone andoptionally in at least a portion of said gradient of polymerizationzone; in other embodiments, the optically transparent member comprises asemipermeable member, and is configured to contain a sufficient amount(or “pool”) of inhibitor to continuously maintain the dead zone for asufficient length of time, to produce the article being fabricatedwithout additional feeding of inhibitor during the process (which “pool”may be replenished or recharged between production runs). In someembodiments, the optically transparent member is comprised of asemipermeable fluoropolymer, a rigid gas-permeable polymer, porousglass, or a combination thereof. In some embodiments, the irradiatingstep is carried out with a two-dimensional radiation pattern projectedinto said build region, wherein said pattern varies over time while saidconcurrently advancing step continues for a time sufficient to form saidthree-dimensional object (i.e., during which time said gradient ofpolymerization zone is maintained).

While the dead zone and the gradient of polymerization zone do not havea strict boundary therebetween (in those locations where the two meet),the thickness of the gradient of polymerization zone is in someembodiments at least as great as the thickness of the dead zone. Thus,in some embodiments, the dead zone has a thickness of from 0.01, 0.1, 1,2, or 10 microns up to 100, 200 or 400 microns, or more, and/or saidgradient of polymerization zone and said dead zone together have athickness of from 1 or 2 microns up to 400, 600, or 1000 microns, ormore. In some embodiments, the gradient of polymerization zone ismaintained (while polymerizing steps continue) for a time of at least 5,10, 15, 20 or 30 seconds, up to 5, 10, 15 or 20 minutes or more, oruntil completion of the three-dimensional product.

The method may further comprise the step of disrupting said gradient ofpolymerization zone for a time sufficient to form a cleavage line insaid three-dimensional object (e.g., at a predetermined desired locationfor intentional cleavage, or at a location in said object whereprevention of cleavage or reduction of cleavage is non-critical), andthen reinstating said gradient of polymerization zone (e.g. by pausing,and resuming, the advancing step, increasing, then decreasing, theintensity of irradiation, and combinations thereof).

The method may further comprise heating said polymerizable liquid as itis supplied to the build region and/or within the build region (e.g., byan amount as given in the Examples below) to reduce the viscositythereof in the build region (e.g., by an amount as given in the Examplesbelow).

The method may be carried out and the apparatus implemented wherein saidcarrier has at least one channel formed therein, and said filling stepis carried out by passing or forcing said polymerizable liquid into saidbuild region through said at least one channel (e.g., wherein saidcarrier has a plurality of channels formed therein, and whereindifferent polymerizable liquids are forced through different ones ofsaid plurality of channels; e.g., further comprising concurrentlyforming at least one, or a plurality of, external feed conduits separatefrom said object, each of said at least one feed conduits in fluidcommunication with a channel in said carrier, to supply at least one, ora plurality of different, polymerizable liquids from said carrier tosaid build zone). In some embodiments, the semipermeable member has athickness of from 0.1 or 1 millimeters to 10 or 100 millimeters; and/orsaid semipermeable member has a permeability to oxygen of at least 10Barrers.

One particular aspect of the present invention is a method of forming athree-dimensional object, comprising the steps of:

(a) providing a carrier and a build plate, the build plate comprising asemipermeable member, the semipermeable member comprising a buildsurface with the build surface and the carrier defining a build regiontherebetween, and with the build surface in fluid communication by wayof the semipermeable member with a source of polymerization inhibitor;

(b) filling the build region with a polymerizable liquid, thepolymerizable liquid contacting the build surface;

(c) irradiating the build region through the build plate to produce asolid polymerized region in the build region, while forming ormaintaining a liquid film release layer comprised of the polymerizableliquid formed between the solid polymerized region and the buildsurface, the polymerization of which liquid film is inhibited by thepolymerization inhibitor; and

(d) advancing the carrier with the polymerized region adhered theretoaway from the build surface on the build plate to create a subsequentbuild region between the polymerized region and the build surface;

(e) wherein the carrier has at least one channel formed therein, and thefilling step is carried out by passing or forcing the polymerizableliquid into the build region through the at least one channel.

In some embodiments of the foregoing, the carrier has a plurality ofchannels formed therein, and wherein different polymerizable liquids areforced through different ones of the plurality of channels.

In some embodiments of the foregoing, the method further comprisesconcurrently forming at least one, or a plurality of, external feedconduits separate from the object, each of the at least one feedconduits in fluid communication with a channel in the carrier, to supplyat least one, or a plurality of different, polymerizable liquids fromthe carrier to the build zone.

In some embodiments, the method may further comprise: (e) continuingand/or repeating steps (b) through (e) to produce a subsequentpolymerized region adhered to a previous polymerized region until thecontinued or repeated deposition of polymerized regions adhered to oneanother forms the three-dimensional object.

In some embodiments, steps (b) through (e) are carried out concurrently.

In some embodiments, the build plate is substantially fixed orstationary.

In some embodiments, the source of polymerization inhibitor is areservoir of polymerization inhibitor within the semipermeable member.

In some embodiments, the semipermeable member further comprises a feedsurface separate from the build surface.

In some embodiments, the the feed surface is in fluid contact with apolymerization inhibitor so as to provide the source of polymerizationinhibitor.

In some embodiments, the method further comprises heating thepolymerizable liquid to reduce the viscosity thereof in the buildregion.

In some embodiments, the method further comprises cooling thepolymerizable liquid in the build region to dissipate heat generated bypolymerization reactions.

In some embodiments, the the advancing step or steps is/are carried outat a cumulative rate of at least 0.1, 1, 10, 100 or 1000 microns persecond.

In some embodiments, excess polymerizable liquid is supplied to thebuild region, removed or drained therefrom to cool the build region, andthen optionally recirculated back to the build region.

In some embodiments, the advancing step is carried out by advancing thecarrier vertically from the build surface.

In some embodiments, the semipermeable member comprises a top surfaceportion, a bottom surface portion, and an edge surface portion; thebuild surface is on the top surface portion; and the feed surface is onat least one of the top surface portion, the bottom surface portion, andthe edge surface portion.

In some embodiments, the semipermeable member has a thickness of from0.1 or 1 millimeters to 10 or 100 millimeters; and/or the semipermeablemember has a permeability to oxygen of at least 7.5×10⁻¹⁷ m²s⁻¹Pa⁻¹ (10Barrers); and/or the semipermeable member is formed of a semipermeablefluoropolymer, a rigid gas-permeable polymer, porous glass, or acombination thereof.

In some embodiments, the irradiating step is carried out with actinicradiation.

In some embodiments, the carrier has a soluble sacrificial layerthereon, and the three-dimensional object is formed on the solublesacrificial layer.

In some embodiments, the total surface area of the build region occupiesat least seventy percent of the total surface area of the build surface;and/or lateral movement of the carrier and object in any direction isnot more than thirty percent of the width of the build region in thecorresponding direction.

In some embodiments, the polymerizable liquid comprises a free radicalpolymerizable liquid and the inhibitor comprises oxygen.

In some embodiments, the polymerizable liquid comprises anacid-catalyzed or cationically polymerizable liquid, and the inhibitorcomprises a base.

In some embodiments, the polymerizable liquid further comprises anactive agent, a detectable agent, solid particles, or a combinationthereof.

In some embodiments, the three-dimensional object comprises a medicaldevice, rod or fibre.

In some embodiments, the irradiating step is carried out by masklessphotolithography.

In some embodiments, the method further comprises the steps of:monitoring or detecting at least one process parameter and/or providingat least one known or predetermined process parameter; and then alteringat least one process condition in response to the monitored processparameter or known process parameter.

In some embodiments, the carrier with the polymerized region adheredthereto is unidirectionally advanced away from the build surface on thestationary build plate.

A further particular aspect of the invention is an apparatus for forminga three-dimensional object from a polymerizable liquid, comprising: (a)a support; (b) a carrier operatively associated with the support onwhich carrier the three-dimensional object is formed; (c) at least onechannel formed in the carrier; (d) a build plate connected to thesupport, the build plate comprising a semipermeable member, thesemipermeable member comprising a build surface, with the build surfaceand the carrier defining a build region therebetween; (e) a liquidpolymer supply operatively associated with the build plate andconfigured to supply liquid polymer through the at least one channelinto the build region for solidification/polymerization; (f) a radiationsource operatively associated with the build plate and configured toirradiate the build region through the build plate and form a solidpolymerized region therein from the liquid polymer; and (g) the buildsurface being in fluid communication by way of the semipermeable memberwith a source of polymerization inhibitor so as to promote formation ormaintenance of a liquid film release layer of comprised of thepolymerizable liquid formed between the solid polymerized region and thebuild surface, the polymerization of which liquid film is inhibited bythe polymerization inhibitor.

In some embodiments of the foregoing, the carrier has a plurality ofchannels formed therein, configured for supply of differentpolymerizable liquids through different ones of the plurality ofchannels.

In some embodiments, the apparatus further comprises the apparatusfurther comprising at least one, or a plurality of, external feedconduits separate from the object (e.g., which may be constructed in thecourse of fabricating the object), each of the at least one feedconduits in fluid communication with a channel in the carrier,configured for supply of at least one, or a plurality of different,polymerizable liquids from the carrier to the build zone.

In some embodiments of the foregoing, the build plate is substantiallyfixed or stationary.

In some embodiments of the foregoing, the source of polymerizationinhibitor is a reservoir of polymerization inhibitor within thesemipermeable member.

In some embodiments of the foregoing, the semipermeable member furthercomprises a feed surface separate from the build surface.

In some embodiments of the foregoing, the feed surface is in fluidcontact with a polymerization inhibitor so as to provide the source ofpolymerization inhibitor.

In some embodiments of the foregoing, the apparatus further comprises acontroller operatively associated with the carrier and the light sourcefor advancing the carrier away from the build plate during or afterpolymerization of liquid in the build region.

In some embodiments of the foregoing, the apparatus further comprises aheater operatively associated with the build plate and/or the liquidpolymer supply, the heater configured to heat polymerizable liquidsupplied into the build region.

In some embodiments of the foregoing, the apparatus further comprises acooler operatively associated with the build plate and configured tocool polymerizable liquid in the build region.

In some embodiments of the foregoing, the semipermeable member comprisesa top surface portion, a bottom surface portion, and an edge surfaceportion; the build surface is on the top surface portion; and the feedsurface is on at least one of the top surface portion, the bottomsurface portion, and the edge surface portion.

Some embodiments of the foregoing further comprise a pressure sourceoperatively associated with the liquid polymer supply.

In some embodiments of the foregoing, the radiation source comprises alight source.

Some embodiments of the foregoing further comprise a spatial lightmodulation array operatively associated with the radiation source andthe controller and configured to carry out irradiation of thepolymerizable liquid by maskless photolithography.

In some embodiments of the foregoing, the carrier comprises a plate,post, web, film, reel, or combination thereof operatively associatedwith at least one actuator.

In some embodiments of the foregoing, the carrier comprises a drive, thedrive and the controller configured to advance the carrierunidirectionally away from the build surface.

In some embodiments of the foregoing, the carrier has a solublesacrificial layer thereon, and the three-dimensional object is formed onthe soluble sacrificial layer.

In the B9Creator™ 3-dimensional printer, a polydimethylsiloxane (PDMS)coating is applied to the sliding build surface. The PDMS coating issaid to absorb oxygen and create a thin lubricating film ofunpolymerized resin through its action as a polymerization inhibitor.However, the PDMS coated build surface is directly replenished withoxygen by mechanically moving (sliding) the surface from beneath thegrowing object, while wiping unpolymerized resin therefrom with a wiperblade, and then returning it to its previous position beneath thegrowing object. While in some embodiments auxiliary means of providingan inhibitor such as oxygen are provided (e.g., a compressor toassociated channels), the process still employs a layer-by-layerapproach with sliding and wiping of the surface. Since the PDMS coatingmay be swollen by the resin, this swelling, along with these mechanicalsteps, may result in tearing of or damage to the PDMS coating.

Non-limiting examples and specific embodiments of the present inventionare explained in greater detail in the drawings herein and thespecification set forth below. The disclosure of all United StatesPatent references cited herein are to be incorporated herein byreference in their entirety.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic illustration of one embodiment of a method of thepresent invention.

FIG. 2 is a perspective view of one embodiment of an apparatus of thepresent invention.

FIG. 3A provides a side sectional view of a first alternate embodimentof a rigid build plate for use in the present invention.

FIG. 3B provides a side sectional view of a second alternate embodimentof a rigid build plate for use in the present invention.

FIG. 4 illustrates various alternate carriers for use in the presentinvention.

FIG. 5A schematically illustrates a polymerization inhibitor in a rigidbuild plate aiding to establish a non-polymerized film on the surfacethereof.

FIG. 5B illustrates the embodiment of FIG. 5A, with application of UVradiation.

FIG. 5C illustrates the embodiment of FIGS. 5A-5B, after separation ofthe two plates.

FIG. 5D illustrates an experiment similar to FIGS. 5A to 5C, except thatclean glass is employed.

FIG. 5E illustrates the embodiment of FIG. 5D, with application of UVradiation.

FIG. 5F illustrates the embodiment of FIGS. 5D to 5E, after separationof the two plates.

FIG. 5G illustrates an experiment similar to FIGS. 5A to 5C, and FIGS.5D to 54, except that glass treated with a release layer was used.

FIG. 5H illustrates the embodiment of FIG. 5G, with application of UVradiation.

FIG. 5I illustrates the embodiment of FIGS. 5G to 5H, after separationof the two plates.

FIG. 6A schematically illustrates a structure for showing the migrationof an inhibitor (in this case oxygen) through a build plate from a feedsurface on the back of the plate to a build surface on the front of aplate to aid in establishing a non-polymerized film on the buildsurface.

FIG. 6B shows the structure of a pair of samples of FIG. 6A beingexposed to a nitrogen environment.

FIG. 6C shows the structure of one sample of FIG. 6B being exposed to UVradiation immediately after being taken from the nitrogen environment.

FIG. 6D shows separation of the structure of FIG. 6C, with the adhesivecompletely cured.

FIG. 6E shows the structure of a second sample of FIG. 6B being exposedto UV radiation, ten minutes after being taken from the nitrogenenvironment, during which time the sample was exposed to an atmosphereenvironment.

FIG. 6F shows separation of the structure of FIG. 6F, with the adhesiveonly cured adjacent the metal plate.

FIG. 7 schematically illustrates a growing three-dimensional objectbeing advanced away from a build surface, and the gap that must befilled therebetween before subsequent polymerization can be carried out.

FIG. 8 schematically illustrates an embodiment of the invention whichprovides for the application of pressure to speed the filling of the gapshown in FIG. 8.

FIG. 9 illustrates a rod or fiber that can be produced by the methodsand apparatus of the present invention.

FIG. 10 is a photograph of a microneedle array fabricated with methodsand apparatus of the present invention. The diameter of the carrier onwhich the array is held is approximately the same as a United Statestwenty-five cent coin (or “quarter”). Essentially the same carrier isused in the additional examples illustrated below.

FIG. 11 is a photograph of a second microneedle array fabricated withmethods and apparatus of the present invention.

FIG. 12 is a photograph of a ring structure being fabricated withmethods and apparatus of the present invention. Note the extensive“overhang” during fabrication.

FIG. 13 is a photograph of the completed ring of FIG. 12.

FIG. 14 is a photograph of four chess piece structures fabricated withmethods and apparatus of the present invention.

FIG. 15 is a photograph of a rectangular prism structure fabricated withmethods and apparatus of the present invention.

FIG. 16 is a photograph of a coil structure fabricated by methods andapparatus of the present invention. Note the extensive “overhang” duringfabrication through to the completed structure.

FIG. 17 illustrates the effects of dye and photoinitiator on cure time.

FIG. 18 is a photograph of a chess piece similar to those shown FIG. 14above, but made with a dyed resin by the methods of the presentinvention.

FIG. 19 schematically illustrates the fabrication of a plurality ofarticles on the carrier, the carrier having a release layer thereon.

FIG. 20 schematically illustrates the release of a plurality of articlesfrom the carrier with a release layer.

FIG. 21 is a photograph of an array of prisms fabricated by methods andapparatus of the present invention, on a release layer.

FIG. 22 is a photograph of the prisms shown in FIG. 21 after release.

FIG. 23 is a photograph of a cylindrical caged structure produced bymethods and apparatus of the present invention.

FIG. 24 is a photograph of an array similar to that of FIG. 21, andproduced by essentially the same methods, except that it comprises apolyethylene glycol polymer.

FIG. 25 is a photograph of a cylindrical cage structure similar to thatof FIG. 23, and produced by substantially the same methods, except thatit comprises a polyethylene glycol polymer. The part was noted to beflexible.

FIG. 26 schematically illustrates an embodiment of an apparatus of thepresent invention in which one or more heaters are included to reducethe viscosity of the polymerizable liquid.

FIG. 27 schematically illustrates an embodiment of an apparatus of thepresent invention in which the build region is filled with polymerizableliquid fed through the carrier.

FIG. 28 schematically illustrates an embodiment of the invention inwhich external conduits are formed to facilitate feeding one or multiplepolymerizable liquids from the carrier to the build region.

FIG. 29 is a first flow chart illustrating control systems and methodsfor carrying out the present invention.

FIG. 30 is a second flow chart illustrating control systems and methodsfor carrying out the present invention.

FIG. 31 is a third flow chart illustrating control systems and methodsfor carrying out the present invention.

DETAILED DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS

The present invention is now described more fully hereinafter withreference to the accompanying drawings, in which embodiments of theinvention are shown. This invention may, however, be embodied in manydifferent forms and should not be construed as limited to theembodiments set forth herein; rather these embodiments are provided sothat this disclosure will be thorough and complete and will fully conveythe scope of the invention to those skilled in the art.

Like numbers refer to like elements throughout. In the figures, thethickness of certain lines, layers, components, elements or features maybe exaggerated for clarity. Where used, broken lines illustrate optionalfeatures or operations unless specified otherwise.

The terminology used herein is for the purpose of describing particularembodiments only and is not intended to be limiting of the invention. Asused herein, the singular forms “a,” “an” and “the” are intended toinclude plural forms as well, unless the context clearly indicatesotherwise. It will be further understood that the terms “comprises” or“comprising,” when used in this specification, specify the presence ofstated features, integers, steps, operations, elements components and/orgroups or combinations thereof, but do not preclude the presence oraddition of one or more other features, integers, steps, operations,elements, components and/or groups or combinations thereof.

As used herein, the term “and/or” includes any and all possiblecombinations or one or more of the associated listed items, as well asthe lack of combinations when interpreted in the alternative (“or”).

Unless otherwise defined, all terms (including technical and scientificterms) used herein have the same meaning as commonly understood by oneof ordinary skill in the art to which this invention belongs. It will befurther understood that terms, such as those defined in commonly useddictionaries, should be interpreted as having a meaning that isconsistent with their meaning in the context of the specification andclaims and should not be interpreted in an idealized or overly formalsense unless expressly so defined herein. Well-known functions orconstructions may not be described in detail for brevity and/or clarity.

It will be understood that when an element is referred to as being “on,”“attached” to, “connected” to, “coupled” with, “contacting,” etc.,another element, it can be directly on, attached to, connected to,coupled with and/or contacting the other element or intervening elementscan also be present. In contrast, when an element is referred to asbeing, for example, “directly on,” “directly attached” to, “directlyconnected” to, “directly coupled” with or “directly contacting” anotherelement, there are no intervening elements present. It will also beappreciated by those of skill in the art that references to a structureor feature that is disposed “adjacent” another feature can have portionsthat overlap or underlie the adjacent feature.

Spatially relative terms, such as “under,” “below,” “lower,” “over,”“upper” and the like, may be used herein for ease of description todescribe an element's or feature's relationship to another element(s) orfeature(s) as illustrated in the figures. It will be understood that thespatially relative terms are intended to encompass differentorientations of the device in use or operation in addition to theorientation depicted in the figures. For example, if the device in thefigures is inverted, elements described as “under” or “beneath” otherelements or features would then be oriented “over” the other elements orfeatures. Thus the exemplary term “under” can encompass both anorientation of over, and under. The device may otherwise be oriented(rotated 90 degrees or at other orientations) and the spatially relativedescriptors used herein interpreted accordingly. Similarly, the terms“upwardly,” “downwardly,” “vertical,” “horizontal” and the like are usedherein for the purpose of explanation only, unless specificallyindicated otherwise.

It will be understood that, although the terms first, second, etc., maybe used herein to describe various elements, components, regions, layersand/or sections, these elements, components, regions, layers and/orsections should not be limited by these terms. Rather, these terms areonly used to distinguish one element, component, region, layer and/orsection, from another element, component, region, layer and/or section.Thus, a first element, component, region, layer or section discussedherein could be termed a second element, component, region, layer orsection without departing from the teachings of the present invention.The sequence of operations (or steps) is not limited to the orderpresented in the claims or figures unless specifically indicatedotherwise.

1. Polymerizable Liquids.

Any suitable polymerizable liquid can be used to enable the presentinvention. The liquid (sometimes also referred to as “liquid resin”“ink,” or simply “resin” herein) can include a monomer, particularlyphotopolymerizable and/or free radical polymerizable monomers, and asuitable initiator such as a free radical initiator, and combinationsthereof. Examples include, but are not limited to, acrylics,methacrylics, acrylamides, styrenics, olefins, halogenated olefins,cyclic alkenes, maleic anhydride, alkenes, alkynes, carbon monoxide,functionalized oligomers, multifunctional cute site monomers,functionalized PEGs, etc., including combinations thereof. Examples ofliquid resins, monomers and initiators include but are not limited tothose set forth in U.S. Pat. Nos. 8,232,043; 8,119,214; 7,935,476;7,767,728; 7,649,029; WO 2012129968 A1; CN 102715751 A; JP 2012210408 A.

Acid Catalyzed Polymerizable Liquids.

While in some embodiments as noted above the polymerizable liquidcomprises a free radical polymerizable liquid (in which case aninhibitor may be oxygen as described below), in other embodiments thepolymerizable liquid comprises an acid catalyzed, or cationicallypolymerized, polymerizable liquid. In such embodiments the polymerizableliquid comprises monomers contain groups suitable for acid catalysis,such as epoxide groups, vinyl ether groups, etc. Thus suitable monomersinclude olefins such as methoxyethene, 4-methoxystyrene, styrene,2-methylprop-1-ene, 1,3-butadiene, etc.; heterocycloic monomers(including lactones, lactams, and cyclic amines) such as oxirane,thietane, tetrahydrofuran, oxazoline, 1,3, dioxepane, oxetan-2-one,etc., and combinations thereof. A suitable (generally ionic ornon-ionic) photoacid generator (PAG) is included in the acid catalyzedpolymerizable liquid, examples of which include, but are not limited toonium salts, sulfonium and iodonium salts, etc., such as diphenyl iodidehexafluorophosphate, diphenyl iodide hexafluoroarsenate, diphenyl iodidehexafluoroantimonate, diphenyl p-methoxyphenyl triflate, diphenylp-toluenyl triflate, diphenyl p-isobutylphenyl triflate, diphenylp-tert-butylphenyl triflate, triphenylsulfonium hexafluororphosphate,triphenylsulfonium hexafluoroarsenate, triphenylsulfoniumhexafluoroantimonate, triphenylsulfonium triflate,dibutylnaphthylsulfonium triflate, etc., including mixtures thereof.See, e.g., U.S. Pat. Nos. 7,824,839; 7,550,246; 7,534,844; 6,692,891;5,374,500; and 5,017,461; see also Photoacid Generator Selection Guidefor the electronics industry and energy curable coatings (BASF 2010).

Hydrogels.

In some embodiments suitable resins includes photocurable hydrogels likepoly(ethylene glycols) (PEG) and gelatins. PEG hydrogels have been usedto deliver a variety of biologicals, including Growth factors; however,a great challenge facing PEG hydrogels crosslinked by chain growthpolymerizations is the potential for irreversible protein damage.Conditions to maximize release of the biologicals from photopolymerizedPEG diacrylate hydrogels can be enhanced by inclusion of affinitybinding peptide sequences in the monomer resin solutions, prior tophotopolymerization allowing sustained delivery. Gelatin is a biopolymerfrequently used in food, cosmetic, pharmaceutical and photographicindustries. It is obtained by thermal denaturation or chemical andphysical degradation of collagen. There are three kinds of gelatin,including those found in animals, fish and humans. Gelatin from the skinof cold water fish is considered safe to use in pharmaceuticalapplications. UV or visible light can be used to crosslink appropriatelymodified gelatin. Methods for crosslinking gelatin include curederivatives from dyes such as Rose Bengal.

Photocurable Silicone Resins.

A suitable resin includes photocurable silicones. UV cure siliconerubber, such as Siliopren™ UV Cure Silicone Rubber can be used as canLOCTITE™ Cure Silicone adhesives sealants. Applications include opticalinstruments, medical and surgical equipment, exterior lighting andenclosures, electrical connectors/sensors, fiber optics and gaskets.

Biodegradable Resins.

Biodegradable resins are particularly important for implantable devicesto deliver drugs or for temporary performance applications, likebiodegradable screws and stents (U.S. Pat. Nos. 7,919,162; 6,932,930).Biodegradable copolymers of lactic acid and glycolic acid (PLGA) can bedissolved in PEG dimethacrylate to yield a transparent resin suitablefor use. Polycaprolactone and PLGA oligomers can be functionalized withacrylic or methacrylic groups to allow them to be effective resins foruse.

Photocurable Polyurethanes.

A particularly useful resin is photocurable polyurethanes. Aphotopolymerizable polyurethane composition comprising (1) apolyurethane based on an aliphatic diisocyanate, poly(hexamethyleneisophthalate glycol) and, optionally, 1,4-butanediol; (2) apolyfunctional acrylic ester; (3) a photoinitiator; and (4) ananti-oxidant, can be formulated so that it provides a hard,abrasion-resistant, and stain-resistant material (U.S. Pat. No.4,337,130). Photocurable thermoplastic polyurethane elastomersincorporate photoreactive diacetylene diols as chain extenders.

High Performance Resins.

In some embodiments, high performance resins are used. Such highperformance resins may sometimes require the use of heating to meltand/or reduce the viscosity thereof, as noted above and discussedfurther below. Examples of such resins include, but are not limited to,resins for those materials sometimes referred to as liquid crystallinepolymers of esters, ester-imide, and ester-amide oligomers, as describedin U.S. Pat. Nos. 7,507,784; 6,939,940. Since such resins are sometimesemployed as high-temperature thermoset resins, in the present inventionthey further comprise a suitable photoinitiator such as benzophenone,anthraquinone, amd fluoroenone initiators (including derivativesthereof), to initiate cross-linking on irradiation, as discussed furtherbelow.

Additional Example Resins.

Particularly useful resins for dental applications include EnvisionTEC'sClear Guide, EnvisionTEC's E-Denstone Material. Particularly usefulresins for hearing aid industries include EnvisionTEC's e-Shell 300Series of resins. Particularly useful resins include EnvisionTEC'sHTM140IV High Temperature Mold Material for use directly with vulcanizedrubber in molding/casting applications. A particularly useful materialfor making tough and stiff parts includes EnvisionTEC's RC31 resin. Aparticularly useful resin for investment casting applications includesEnvisionTEC's Easy Cast EC500.

Additional Resin Ingredients.

The liquid resin or polymerizable material can have solid particlessuspended or dispersed therein. Any suitable solid particle can be used,depending upon the end product being fabricated. The particles can bemetallic, organic/polymeric, inorganic, or composites or mixturesthereof. The particles can be nonconductive, semi-conductive, orconductive (including metallic and non-metallic or polymer conductors);and the particles can be magnetic, ferromagnetic, paramagnetic, ornonmagnetic. The particles can be of any suitable shape, includingspherical, elliptical, cylindrical, etc. The particles can comprise anactive agent or detectable compound as described below, though these mayalso be provided dissolved solubilized in the liquid resin as alsodiscussed below. For example, magnetic or paramagnetic particles ornanoparticles can be employed.

The liquid resin can have additional ingredients solubilized therein,including pigments, dyes, active compounds or pharmaceutical compounds,detectable compounds (e.g., fluorescent, phosphorescent, radioactive),etc., again depending upon the particular purpose of the product beingfabricated. Examples of such additional ingredients include, but are notlimited to, proteins, peptides, nucleic acids (DNA, RNA) such as siRNA,sugars, small organic compounds (drugs and drug-like compounds), etc.,including combinations thereof.

Inhibitors of Polymerization.

Inhibitors or polymerization inhibitors for use in the present inventionmay be in the form of a liquid or a gas. In some embodiments, gasinhibitors are preferred. The specific inhibitor will depend upon themonomer being polymerized and the polymerization reaction. For freeradical polymerization monomers, the inhibitor can conveniently beoxygen, which can be provided in the form of a gas such as air, a gasenriched in oxygen (optionally but in some embodiments preferablycontaining additional inert gases to reduce combustibility thereof), orin some embodiments pure oxygen gas. In alternate embodiments, such aswhere the monomer is polymerized by photoacid generator initiator, theinhibitor can be a base such as ammonia, trace amines (e.g. methylamine, ethyl amine, di and trialkyl amines such as dimethyl amine,diethyl amine, trimethyl amine, triethyl amine, etc.), or carbondioxide, including mixtures or combinations thereof.

Polymerizable Liquids Carrying Live Cells.

In some embodiments, the polymerizable liquid may carry live cells as“particles” therein. Such polymerizable liquids are generally aqueous,and may be oxygenated, and may be considered as “emulsions” where thelive cells are the discrete phase. Suitable live cells may be plantcells (e.g., monocot, dicot), animal cells (e.g., mammalian, avian,amphibian, reptile cells), microbial cells (e.g., prokaryote, eukaryote,protozoal, etc.), etc. The cells may be of differentiated cells from orcorresponding to any type of tissue (e.g., blood, cartilage, bone,muscle, endocrine gland, exocrine gland, epithelial, endothelial, etc.),or may be undifferentiated cells such as stem cells or progenitor cells.In such embodiments the polymerizable liquid can be one that forms ahydrogel, including but not limited to those described in U.S. Pat. Nos.7,651,683; 7,651,682; 7,556,490; 6,602,975; 5,836,313; etc.

2. Apparatus.

A non-limiting embodiment of an apparatus of the invention is shown inFIG. 2. It comprises a radiation source 11 such as a digital lightprocessor (DLP) providing electromagnetic radiation 12 which thoughreflective mirror 13 illuminates a build chamber defined by wall 14 anda rigid build plate 15 forming the bottom of the build chamber, whichbuild chamber is filled with liquid resin 16. The bottom of the chamber15 is constructed of rigid build plate comprising a rigid semipermeablemember as discussed further below. The top of the object underconstruction 17 is attached to a carrier 18. The carrier is driven inthe vertical direction by linear stage 19, although alternate structurescan be used as discussed below.

A liquid resin reservoir, tubing, pumps liquid level sensors and/orvalves can be included to replenish the pool of liquid resin in thebuild chamber (not shown for clarity) though in some embodiments asimple gravity feed may be employed. Drives/actuators for the carrier orlinear stage, along with associated wiring, can be included inaccordance with known techniques (again not shown for clarity). Thedrives/actuators, radiation source, and in some embodiments pumps andliquid level sensors can all be operatively associated with a suitablecontroller, again in accordance with known techniques.

Build plates 15 used to carry out the present invention generallycomprise or consist of a (typically rigid or solid, stationary, and/orfixed) semipermeable (or gas permeable) member, alone or in combinationwith one or more additional supporting substrates (e.g., clamps andtensioning members to rigidify an otherwise flexible semipermeablematerial). The rigid semipermeable member can be made of any suitablematerial that is optically transparent at the relevant wavelengths (orotherwise transparent to the radiation source, whether or not it isvisually transparent as perceived by the human eye—i.e., an opticallytransparent window may in some embodiments be visually opaque),including but not limited to porous or microporous glass, and the rigidgas permeable polymers used for the manufacture of rigid gas permeablecontact lenses. See, e.g., Norman G. Gaylord, U.S. Pat. No. RE31,406;see also U.S. Pat. Nos. 7,862,176; 7,344,731; 7,097,302; 5,349,394;5,310,571; 5,162,469; 5,141,665; 5,070,170; 4,923,906; and 4,845,089. Insome embodiments such materials are characterized as glassy and/oramorphous polymers and/or substantially crosslinked that they areessentially non-swellable. Preferably the rigid semipermeable member isformed of a material that does not swell when contacted to the liquidresin or material to be polymerized (i.e., is “non-swellable”). Suitablematerials for the rigid semipermeable member include rigid amorphousfluoropolymers, such as those described in U.S. Pat. Nos. 5,308,685 and5,051,115. For example, such fluoropolymers are particularly useful oversilicones that would potentially swell when used in conjunction withorganic liquid resin inks to be polymerized. For some liquid resin inks,such as more aqueous-based monomeric systems and/or some polymeric resinink systems that have low swelling tendencies, silicone based windowmaterials maybe suitable. The solubility or permeability of organicliquid resin inks can be dramatically decreased by a number of knownparameters including increasing the crosslink density of the windowmaterial or increasing the molecular weight of the liquid resin ink. Insome embodiments the build plate may be formed from a thin film or sheetof material which is flexible when separated from the apparatus of theinvention, but which is clamped and tensioned when installed in theapparatus (e.g., with a tensioning ring) so that it is rendered rigid inthe apparatus. Particular materials include TEFLON AF® fluoropolymers,commercially available from DuPont. Additional materials includeperfluoropolyether polymers such as described in U.S. Pat. Nos.8,268,446; 8,263,129; 8,158,728; and 7,435,495.

It will be appreciated that essentially all solid materials, and most ofthose described above, have some inherent “flex” even though they may beconsidered “rigid,” depending on factors such as the shape and thicknessthereof and environmental factors such as the pressure and temperatureto which they are subjected. In addition, the terms “stationary” or“fixed” with respect to the build plate is intended to mean that nomechanical interruption of the process occurs, or no mechanism orstructure for mechanical interruption of the process (as in alayer-by-layer method or apparatus) is provided, even if a mechanism forincremental adjustment of the build plate (for example, adjustment thatdoes not lead to or cause collapse of the gradient of polymerizationzone) is provided).

The semipermeable member typically comprises a top surface portion, abottom surface portion, and an edge surface portion. The build surfaceis on the top surface portion; and the feed surface may be on one, two,or all three of the top surface portion, the bottom surface portion,and/or the edge surface portion. In the embodiment illustrated in FIG. 2the feed surface is on the bottom surface portion, but alternateconfigurations where the feed surface is provided on an edge, and/or onthe top surface portion (close to but separate or spaced away from thebuild surface) can be implemented with routine skill.

The semipermeable member has, in some embodiments, a thickness of from0.01, 0.1 or 1 millimeters to 10 or 100 millimeters, or more (dependingupon the size of the item being fabricated, whether or not it islaminated to or in contact with an additional supporting plate such asglass, etc., as discussed further below.

The permeability of the semipermeable member to the polymerizationinhibitor will depend upon conditions such as the pressure of theatmosphere and/or inhibitor, the choice of inhibitor, the rate or speedof fabrication, etc. In general, when the inhibitor is oxygen, thepermeability of the semipermeable member to oxygen may be from 10 or 20Barrers, up to 1000 or 2000 Barrers, or more. For example, asemipermeable member with a permeability of 10 Barrers used with a pureoxygen, or highly enriched oxygen, atmosphere under a pressure of 150PSI may perform substantially the same as a semipermeable member with apermeability of 500 Barrers when the oxygen is supplied from the ambientatmosphere under atmospheric conditions.

Thus, the semipermeable member may comprise a flexible polymer film(having any suitable thickness, e.g., from 0.001, 0.01, 0.1 or 1millimeters to 5, 10, or 100 millimeters, or more), and the build platemay further comprise a tensioning member (e.g., a peripheral clamp andan operatively associated strain member or stretching member, as in a“drum head”; a plurality of peripheral clamps, etc., includingcombinations thereof) connected to the polymer film and to fix andrigidify the film (e.g., at least sufficiently so that the film does notstick to the object as the object is advanced and resiliently orelastically rebound therefrom). The film has a top surface and a bottomsurface, with the build surface on the top surface and the feed surfacepreferably on the bottom surface. In other embodiments, thesemipermeable member comprises: (i) a polymer film layer (having anysuitable thickness, e.g., from 0.001, 0.01, 0.1 or 1 millimeters to 5,10 or 100 millimeters, or more), having a top surface positioned forcontacting said polymerizable liquid and a bottom surface, and (ii) arigid, gas permeable, optically transparent supporting member (havingany suitable thickness, e.g., from 0.01, 0.1 or 1 millimeters to 10,100, or 200 millimeters, or more), contacting said film layer bottomsurface. The supporting member has a top surface contacting the filmlayer bottom surface, and the supporting member has a bottom surfacewhich may serve as the feed surface for the polymerization inhibitor.Any suitable materials that are semipermeable (that is, permeable to thepolymerization inhibitor) may be used. For example, the polymer film orpolymer film layer may, for example, be a fluoropolymer film, such as anamorphous thermoplastic fluoropolymer like TEFLON AF 1600™ or TEFLON AF2400™ fluoropolymer films, or perfluoropolyether (PFPE), particularly acrosslinked PFPE film, or a crosslinked silicone polymer film. Thesupporting member comprises a silicone or crosslinked silicone polymermember such as a polydmiethylxiloxane member, a rigid gas permeablepolymer member, or a porous or microporous glass member. Films can belaminated or clamped directly to the rigid supporting member withoutadhesive (e.g., using PFPE and PDMS materials), or silane couplingagents that react with the upper surface of a PDMS layer can be utilizedto adhere to the first polymer film layer. UV-curable,acrylate-functional silicones can also be used as a tie layer betweenUV-curable PFPEs and rigid PDMS supporting layers.

As noted above, while in some embodiments the semipermeable memberallows inhibitor to pass therethrough, it can simply be configured tocontain a sufficient amount (or “pool”) of inhibitor to continuouslymaintain the dead zone for a sufficient length of time, to produce thearticle being fabricated without additional feeding of inhibitor duringthe process (which “pool” may be replenished or recharged betweenproduction runs). The size and internal volume of the member can beconfigured as appropriate for the particular article being fabricated tocontain a sufficient pool of inhibitor.

When configured for placement in the apparatus, the carrier defines a“build region” on the build surface, within the total area of the buildsurface. Because lateral “throw” (e.g., in the X and/or Y directions) isnot required in the present invention to break adhesion betweensuccessive layers, as in the Joyce and Chen devices noted previously,the area of the build region within the build surface may be maximized(or conversely, the area of the build surface not devoted to the buildregion may be minimized). Hence in some embodiments, the total surfacearea of the build region can occupy at least fifty, sixty, seventy,eighty, or ninety percent of the total surface area of the buildsurface.

As shown in FIG. 2, the various components are mounted on a support orframe assembly 20. While the particular design of the support or frameassembly is not critical and can assume numerous configurations, in theillustrated embodiment it is comprised of a base 21 to which theradiation source 11 is securely or rigidly attached, a vertical member22 to which the linear stage is operatively associated, and a horizontaltable 23 to which wall 14 is removably or securely attached (or on whichthe wall is placed), and with the build plate rigidly fixed, eitherpermanently or removably, to form the build chamber as described above.

As noted above, the build plate can consist of a single unitary andintegral piece of a rigid semipermeable member, or can compriseadditional materials. For example, as shown in FIG. 3A, a porous ormicroporous glass can be laminated or fixed to a rigid semipermeablematerial. Or, as shown in FIG. 3B, a semipermeable member as an upperportion can be fixed to a transparent lower member having purgingchannels formed therein for feeding gas carrying the polymerizationinhibitor to the semipermeable member (through which it passes to thebuild surface to facilitate the formation of a release layer ofunpolymerized liquid material, as noted above and below). Such purgechannels may extend fully or partially through the base plate: Forexample, the purge channels may extend partially into the base plate,but then end in the region directly underlying the build surface toavoid introduction of distortion. Specific geometries will depend uponwhether the feed surface for the inhibitor into the semipermeable memberis located on the same side or opposite side as the build surface, on anedge portion thereof, or a combination of several thereof.

Any suitable radiation source (or combination of sources) can be used,depending upon the particular resin employed, including electron beamand ionizing radiation sources. In a preferred embodiment the radiationsource is an actinic radiation source, such as one or more lightsources, and in particular one or more ultraviolet light sources. Anysuitable light source can be used, such as incandescent lights,fluorescent lights, phosphorescent or luminescent lights, a laser,light-emitting diode, etc., including arrays thereof. The light sourcepreferably includes a pattern-forming element operatively associatedwith a controller, as noted above. In some embodiments, the light sourceor pattern forming element comprises a digital (or deformable)micromirror device (DMD) with digital light processing (DLP), a spatialmodulator (SLM), or a microelectromechanical system (MEMS) mirror array,a mask (aka a reticle), a silhouette, or a combination thereof. See,U.S. Pat. No. 7,902,526. Preferably the light source comprises a spatiallight modulation array such as a liquid crystal light valve array ormicromirror array or DMD (e.g., with an operatively associated digitallight processor, typically in turn under the control of a suitablecontroller), configured to carry out exposure or irradiation of thepolymerizable liquid without a mask, e.g., by maskless photolithography.See, e.g., U.S. Pat. Nos. 6,312,134; 6,248,509; 6,238,852; and5,691,541.

Alternate carriers and actuator/drive arrangements are shown in FIG. 4.Numerous variations can be employed, including a take-up reel, an XYZdrive assembly (e.g., as commonly used on an automated microscopestage), etc. In the embodiment illustrated in FIG. 2 the drive assemblywill generally comprise a worm gear and motor, a rack and pinion andmotor, a hydraulic, pneumatic, or piezoelectric drive, or the like,adapted to move or advance the carrier away from the build surface inthe vertical or “Z” direction only. In the alternative embodiment shownin FIG. 4 a spool or take-up real can be utilized, with associateddrives or actuators and guides (not shown), particularly when theproduct being fabricated is an elongated rod or fiber (discussed furtherbelow). In an alternate embodiment, a pair of take-up reels withassociated guides, and associated drives or actuators (not shown), canbe mounted on the linear stage to provide movement in either the Xand/or Y direction in addition to or in combination with, movement inthe Z direction provided by linear stage 19. In still other embodiments,an XYZ drive assembly like that used in an automated microscope can beused in place of linear stage 19 to move or advance the carrier awayfrom the build surface in the X, Y, and/or Z direction, e.g., at anangle, or at changing angles, or combinations of directions at variousstages. Thus advancement away from the build plate can be carried outsolely in the Z (or vertical) direction, or in at least the Z direction,by combining movement in the Z direction with movement in the X and/or Ydirections. In some embodiments, there may be movement in the X and/or Ydirections concurrently with movement in the Z direction, with themovement in the X and/or Y direction hence occurring duringpolymerization of the polymerizable liquid (this is in contrast to themovement described in Y. Chen et al., or M. Joyce, supra, which ismovement between prior and subsequent polymerization steps for thepurpose of replenishing polymerizable liquid). In the present inventionsuch movement may be carried out for purposes such as reducing “burn in”or fouling in a particular zone of the build surface.

Because an advantage of some embodiments of the present invention isthat the size of the build surface on the semipermeable member (i.e.,the build plate or window) may be reduced due to the absence of arequirement for extensive lateral “throw” as in the Joyce or Chendevices noted above, in the methods, systems and apparatus of thepresent invention lateral movement (including movement in the X and/or Ydirection or combination thereof) of the carrier and object (if suchlateral movement is present) is preferably not more than, or less than,80, 70, 60, 50, 40, 30, 20, or even 10 percent of the width (in thedirection of that lateral movement) of the build region.

While in some embodiments the carrier is mounted on an elevator toadvance up and away from a stationary build plate, on other embodimentsthe converse arrangement may be used: That is, the carrier may be fixedand the build plate lowered to thereby advance the carrier awaytherefrom. Numerous different mechanical configurations will be apparentto those skilled in the art to achieve the same result, in all of whichthe build plate is “stationary” in the sense that no lateral (X or Y)movement is required to replenish the inhibitor thereon, or no elasticbuild plate that must be stretched and then rebound (with associatedover-advance, and back-up of, the carrier) need be employed.

Depending on the choice of material from which the carrier isfabricated, and the choice of polymer or resin from which the article ismade, adhesion of the article to the carrier may sometimes beinsufficient to retain the article on the carrier through to completionof the finished article or “build.” For example, an aluminum carrier mayhave lower adhesion than a poly(vinyl chloride) (or “PVC”) carrier.Hence one solution is to employ a carrier comprising a PVC on thesurface to which the article being fabricated is polymerized. If thispromotes too great an adhesion to conveniently separate the finishedpart from the carrier, then any of a variety of techniques can be usedto further secure the article to a less adhesive carrier, including butnot limited to the application of adhesive tape such as “Greener MaskingTape for Basic Painting #2025 High adhesion” to further secure thearticle to the carrier during fabrication.

Soluble Sacrificial Layers.

In some embodiments, a soluble sacrificial layer or release layer may beestablished between the carrier and the three-dimensional object, sothat that sacrificial layer may be subsequently solubilized toconveniently release the three-dimensional object from the carrier oncefabrication is complete. Any suitable sacrificial layer, such as anadhesive, that may be coated or otherwise provided on the carrier may beemployed, and any suitable solvent (e.g., polar and non-polar organicsolvents, aqueous solvents, etc. to solubilize the sacrificial releaselayer may be employed, though the sacrificial layer and itscorresponding solvent should be chosen so that the particular materialfrom which the three-dimensional object is formed is not itself undulyattacked or solubilized by that solvent. The sacrificial layer may beapplied to the carrier by any suitable technique, such as spraying, dipcoating, painting, etc. Examples of suitable materials for the solublesacrificial release layer (and non-limiting examples of correspondingsolvents) include but are not limited to: cyanoacrylate adhesive(acetone solvent); poly(vinylpyrrolidone) (water and/or isopropylalcohol solvent); lacquers (acetone solvent); polyvinyl alcohol,polyacrylic acid, poly(methacrylic acid), polyacrylamide, polyalkyleneoxides such as poly(ethylene oxide), sugars and saccharides such assucrose and dextran (all water or aqueous solvents); etc. Lower surfaceenergy solvents are in some embodiments particularly preferred.

In some embodiments of the invention, the actuator/drive and/orassociated controller are configured to only advance the carrier awayfrom the build plate (e.g., is unidirectional), as discussed furtherbelow.

In some embodiments of the invention, the actuator/drive and/orassociated controller are configured as a continuous drive (as opposedto a step-wise drive), as also discussed below.

3. Methods.

As noted above, the present invention provides a method of forming athree-dimensional object, comprising the steps of: (a) providing acarrier and a build plate, said build plate comprising a semipermeablemember, said semipermeable member comprising a build surface and a feedsurface separate from said build surface, with said build surface andsaid carrier defining a build region therebetween, and with said feedsurface in fluid contact with a polymerization inhibitor; then(concurrently and/or sequentially) (b) filing said build region with apolymerizable liquid, said polymerizable liquid contacting said buildsegment, (c) irradiating said build region through said build plate toproduce a solid polymerized region in said build region, with a liquidfilm release layer comprised of said polymerizable liquid formed betweensaid solid polymerized region and said build surface, the polymerizationof which liquid film is inhibited by said polymerization inhibitor; and(d) advancing said carrier with said polymerized region adhered theretoaway from said build surface on said stationary build plate to create asubsequent build region between said polymerized region and said topzone. In general the method includes (e) continuing and/or repeatingsteps (b) through (d) to produce a subsequent polymerized region adheredto a previous polymerized region until the continued or repeateddeposition of polymerized regions adhered to one another forms saidthree-dimensional object.

Since no mechanical release of a release layer is required, or nomechanical movement of a build surface to replenish oxygen is required,the method can be carried out in a continuous fashion, though it will beappreciated that the individual steps noted above may be carried outsequentially, concurrently, or a combination thereof. Indeed, the rateof steps can be varied over time depending upon factors such as thedensity and/or complexity of the region under fabrication.

Also, since mechanical release from a window or from a release layergenerally requires that the carrier be advanced a greater distance fromthe build plate than desired for the next irradiation step, whichenables the window to be recoated, and then return of the carrier backcloser to the build plate (e.g., a “two steps forward one step back”operation), the present invention in some embodiments permitselimination of this “back-up” step and allows the carrier to be advancedunidirectionally, or in a single direction, without intervening movementof the window for re-coating, or “snapping” of a pre-formed elasticrelease-layer.

In some embodiments, the advancing step is carried out sequentially inuniform increments (e.g., of from 0.1 or 1 microns, up to 10 or 100microns, or more) for each step or increment. In some embodiments, theadvancing step is carried out sequentially in variable increments (e.g.,each increment ranging from 0.1 or 1 microns, up to 10 or 100 microns,or more) for each step or increment. The size of the increment, alongwith the rate of advancing, will depend in part upon factors such astemperature, pressure, structure of the article being produced (e.g.,size, density, complexity, configuration, etc.)

In other embodiments of the invention, the advancing step is carried outcontinuously, at a uniform or variable rate.

In some embodiments, the rate of advance (whether carried outsequentially or continuously) is from about 0.11, or 10 microns persecond, up to about to 100, 1,000, or 10,000 microns per second, againdepending again depending on factors such as temperature, pressure,structure of the article being produced, intensity of radiation, etc

As described further below, in some embodiments the filling step iscarried out by forcing said polymerizable liquid into said build regionunder pressure. In such a case, the advancing step or steps may becarried out at a rate or cumulative or average rate of at least 0.1, 1,10, 50, 100, 500 or 1000 microns per second, or more. In general, thepressure may be whatever is sufficient to increase the rate of saidadvancing step(s) at least 2, 4, 6, 8 or 10 times as compared to themaximum rate of repetition of said advancing steps in the absence ofsaid pressure. Where the pressure is provided by enclosing an apparatussuch as described above in a pressure vessel and carrying the processout in a pressurized atmosphere (e.g., of air, air enriched with oxygen,a blend of gasses, pure oxygen, etc.) a pressure of 10, 20, 30 or 40pounds per square inch (PSI) up to, 200, 300, 400 or 500 PSI or more,may be used. For fabrication of large irregular objects higher pressuresmay be less preferred as compared to slower fabrication times due to thecost of a large high pressure vessel. In such an embodiment, both thefeed surface and the polymerizable liquid can be in fluid contact withthe same compressed gas (e.g., one comprising from 20 to 95 percent byvolume of oxygen, the oxygen serving as the polymerization inhibitor.

On the other hand, when smaller items are fabricated, or a rod or fiberis fabricated that can be removed or exited from the pressure vessel asit is produced through a port or orifice therein, then the size of thepressure vessel can be kept smaller relative to the size of the productbeing fabricated and higher pressures can (if desired) be more readilyutilized.

As noted above, the irradiating step is in some embodiments carried outwith patterned irradiation. The patterned irradiation may be a fixedpattern or may be a variable pattern created by a pattern generator(e.g., a DLP) as discussed above, depending upon the particular itembeing fabricated.

When the patterned irradiation is a variable pattern rather than apattern that is held constant over time, then each irradiating step maybe any suitable time or duration depending on factors such as theintensity of the irradiation, the presence or absence of dyes in thepolymerizable material, the rate of growth, etc. Thus in someembodiments each irradiating step can be from 0.001, 0.01, 0.1, 1 or 10microseconds, up to 1, 10, or 100 minutes, or more, in duration. Theinterval between each irradiating step is in some embodiments preferablyas brief as possible, e.g., from 0.001, 0.01, 0.1, or 1 microseconds upto 0.1, 1, or 10 seconds.

In some embodiments the build surface is flat; in other the buildsurface is irregular such as convexly or concavely curved, or has wallsor trenches formed therein. In either case the build surface may besmooth or textured.

Curved and/or irregular build plates or build surfaces can be used infiber or rod formation, to provide different materials to a singleobject being fabricated (that is, different polymerizable liquids to thesame build surface through channels or trenches formed in the buildsurface, each associated with a separate liquid supply, etc.

Carrier Feed Channels for Polymerizable Liquid.

While polymerizable liquid may be provided directly to the build platefrom a liquid conduit and reservoir system, in some embodiments thecarrier include one or more feed channels therein. The carrier feedchannels are in fluid communication with the polymerizable liquidsupply, for example a reservoir and associated pump. Different carrierfeed channels may be in fluid communication with the same supply andoperate simultaneously with one another, or different carrier feedchannels may be separately controllable from one another (for example,through the provision of a pump and/or valve for each). Separatelycontrollable feed channels may be in fluid communication with areservoir containing the same polymerizable liquid, or may be in fluidcommunication with a reservoir containing different polymerizableliquids. Through the use of valve assemblies, different polymerizableliquids may in some embodiments be alternately fed through the same feedchannel, if desired.

4. Controller and Process Control.

The methods and apparatus of the invention can include process steps andapparatus features to implement process control, including feedback andfeed-forward control, to, for example, enhance the speed and/orreliability of the method.

A controller for use in carrying out the present invention may beimplemented as hardware circuitry, software, or a combination thereof.In one embodiment, the controller is a general purpose computer thatruns software, operatively associated with monitors, drives, pumps, andother components through suitable interface, hardware and/or software.Suitable software for the control of a three-dimensional printing orfabrication method and apparatus as described herein includes, but isnot limited to, the ReplicatorG open source 3d printing program,3DPrint™ controller software from 3D systems, Slic3r, Skeinforge,KISSlicer, Repetier-Host, PrintRun, Cura, etc., including combinationsthereof.

Process parameters to directly or indirectly monitor, continuously orintermittently, during the process (e.g., during one, some or all ofsaid filling, irradiating and advancing steps) include, but are notlimited to, irradiation intensity, temperature of carrier, polymerizableliquid in the build zone, temperature of growing product, temperature ofbuild plate, pressure, speed of advance, pressure, force (e.g., exertedon the build plate through the carrier and product being fabricated),strain (e.g., exerted on the carrier by the growing product beingfabricated), thickness of release layer, etc.

Known parameters that may be used in feedback and/or feed-forwardcontrol systems include, but are not limited to, expected consumption ofpolymerizable liquid (e.g., from the known geometry or volume of thearticle being fabricated), degradation temperature of the polymer beingformed from the polymerizable liquid, etc.

Process conditions to directly or indirectly control, continuously orstep-wise, in response to a monitored parameter, and/or known parameters(e.g., during any or all of the process steps noted above), include, butare not limited to, rate of supply of polymerizable liquid, temperature,pressure, rate or speed of advance of carrier, intensity of irradiation,duration of irradiation (e.g. for each “slice”), etc.

For example, the temperature of the polymerizable liquid in the buildzone, or the temperature of the build plate, can be monitored, directlyor indirectly with an appropriate thermocouple, non-contact temperaturesensor (e.g., an infrared temperature sensor), or other suitabletemperature sensor, to determine whether the temperature exceeds thedegradation temperature of the polymerized product. If so, a processparameter may be adjusted through a controller to reduce the temperaturein the build zone and/or of the build plate. Suitable process parametersfor such adjustment may include: decreasing temperature with a cooler,decreasing the rate of advance of the carrier, decreasing intensity ofthe irradiation, decreasing duration of radiation exposure, etc.

In addition, the intensity of the irradiation source (e.g., anultraviolet light source such as a mercury lamp) may be monitored with aphotodetector to detect a decrease of intensity from the irradiationsource (e.g., through routine degradation thereof during use). Ifdetected, a process parameter may be adjusted through a controller toaccommodate the loss of intensity. Suitable process parameters for suchadjustment may include: increasing temperature with a heater, decreasingthe rate of advance of the carrier, increasing power to the lightsource, etc.

As another example, control of temperature and/or pressure to enhancefabrication time may be achieved with heaters and coolers (individually,or in combination with one another and separately responsive to acontroller), and/or with a pressure supply (e.g., pump, pressure vessel,valves and combinations thereof) and/or a pressure release mechanismsuch as a controllable valve (individually, or in combination with oneanother and separately responsive to a controller).

In some embodiments the controller is configured to maintain thegradient of polymerization zone described herein (see, e.g., FIG. 1)throughout the fabrication of some or all of the final product. Thespecific configuration (e.g., times, rate or speed of advancing,radiation intensity, temperature, etc.) will depend upon factors such asthe nature of the specific polymerizable liquid and the product beingcreated. Configuration to maintain the gradient of polymerization zonemay be carried out empirically, by entering a set of process parametersor instructions previously determined, or determined through a series oftest runs or “trial and error”; configuration may be provided throughpre-determined instructions; configuration may be achieved by suitablemonitoring and feedback (as discussed above), combinations thereof, orin any other suitable manner.

5. Fabrication Products.

Three-dimensional products produced by the methods and processes of thepresent invention may be final, finished or substantially finishedproducts, or may be intermediate products subject to furthermanufacturing steps such as surface treatment, laser cutting, electricdischarge machining, etc. Intermediate products include products forwhich further additive manufacturing, in the same or a differentapparatus, may be carried out). For example, a fault or cleavage linemay be introduced deliberately into an ongoing “build” by disrupting,and then reinstating, the gradient of polymerization zone, to terminateone region of the finished product, or simply because a particularregion of the finished product or “build” is less fragile than others.

Numerous different products can be made by the methods and apparatus ofthe present invention, including both large-scale models or prototypes,small custom products, miniature or microminiature products or devices,etc. Examples include, but are not limited to, medical devices andimplantable medical devices such as stents, drug delivery depots,functional structures, microneedle arrays, fibers and rods such aswaveguides, micromechanical devices, microfluidic devices, etc.

Thus in some embodiments the product can have a height of from 0.1 or 1millimeters up to 10 or 100 millimeters, or more, and/or a maximum widthof from 0.1 or 1 millimeters up to 10 or 100 millimeters, or more. Inother embodiments, the product can have a height of from 10 or 100nanometers up to 10 or 100 microns, or more, and/or a maximum width offrom 10 or 100 nanometers up to 10 or 100 microns, or more. These areexamples only: Maximum size and width depends on the architecture of theparticular device and the resolution of the light source and can beadjusted depending upon the particular goal of the embodiment or articlebeing fabricated.

In some embodiments, the ratio of height to width of the product is atleast 2:1, 10:1, 50:1, or 100:1, or more, or a width to height ratio of1:1, 10:1, 50:1, or 100:1, or more.

In some embodiments, the product has at least one, or a plurality of,pores or channels formed therein, as discussed further below.

The processes described herein can produce products with a variety ofdifferent properties. Hence in some embodiments the products are rigid;in other embodiments the products are flexible or resilient. In someembodiments, the products are a solid; in other embodiments, theproducts are a gel such as a hydrogel. In some embodiments, the productshave a shape memory (that is, return substantially to a previous shapeafter being deformed, so long as they are not deformed to the point ofstructural failure). In some embodiments, the products are unitary (thatis, formed of a single polymerizable liquid); in some embodiments, theproducts are composites (that is, formed of two or more differentpolymerizable liquids). Particular properties will be determined byfactors such as the choice of polymerizable liquid(s) employed.

In some embodiments, the product or article made has at least oneoverhanging feature (or “overhang”), such as a bridging element betweentwo supporting bodies, or a cantilevered element projecting from onesubstantially vertical support body. Because of the unidirectional,continuous nature of some embodiments of the present processes, theproblem of fault or cleavage lines that form between layers when eachlayer is polymerized to substantial completion and a substantial timeinterval occurs before the next pattern is exposed, is substantiallyreduced. Hence, in some embodiments the methods are particularlyadvantageous in reducing, or eliminating, the number of supportstructures for such overhangs that are fabricated concurrently with thearticle.

The present invention is explained in greater detail in the followingnon-limiting Examples.

EXAMPLE 1 Inhibitor Transfer to Build Surface from a Separate FeedSurface

A drop of ultraviolet (UV) curable adhesive was placed on a metal plateand covered with 10 mm thick plate of TEFLON® AF fluoropolymer (aamorphous, glassy polymer) as shown in FIG. 5 a. UV radiation wassupplied to the adhesive from the side of Teflon AF as shown in FIG. 5b. After UV exposure the two plates were separated. It was found that noforce was required to separate the two plates. Upon examination of thesamples it was discovered that the adhesive was cured only next to themetal plate, and that a thin film of uncured adhesive was present on theTeflon AF fluoropolymer plate and also on the cured portion of theadhesive as shown in FIG. 5 c.

Two controlled experiments were also performed where clean glass (FIGS.5 d-5 f) and also glass treated with release layer (FIGS. 5 g-5 i) wasused. It was confirmed that considerable force was needed to separateclean glass from the metal and it was found that adhesive remained onthe glass. Less force was needed to separate the treated glass, whileadhesive remained on the metal plate.

The chemical phenomenon which describes the observed behavior is oxygeninhibition of the radical polymerization reaction. In particular, TeflonAF has a very high oxygen permeability coefficient. Constant supply ofoxygen through 10 mm think Teflon AF is sufficient to prevent a thinlayer of acrylate adhesive from polymerization. The thickness of uncuredadhesive layer in the above experiment was on the order of 10 micronsand it can be increased or decreased by varying the amount of photoinitiator present in the adhesive.

EXAMPLE 2 Inhibitor Transfer Through Build Plate to Build Surface

Samples 1 and 2 were prepared in a similar manner wherein a drop of UVcurable adhesive was placed on a metal plate and covered with 10 mmthick plate of TEFLON® AF fluoropolymer as shown in FIG. 6 a. Bothsamples were exposed to a nitrogen environment to eliminate any presenceof oxygen as shown in FIG. 6 b. Next both samples were brought into astandard atmosphere environment and Sample 1 was immediately exposed toUV radiation while Sample 2 was exposed to UV radiation 10 minutes afterbeing in the atmosphere environment. Both samples were exposed to thesame amount of UV radiation as shown in FIG. 6C and FIG. 6E. Uponexamination of the samples after UV exposure it was discovered that theadhesive was cured completely in Sample 1 as shown in FIG. 6D and onlynext to the metal plate in Sample 2 as shown in FIG. 6F. A thin film ofuncured adhesive was present on the Teflon AF fluoropolymer plate andalso on the cured portion of the adhesive for Sample 2. This experimentshows that the inhibitor, oxygen, was transferred through Teflon AFplate to the adhesive during the 10 minute period of being exposed tothe atmosphere environment.

EXAMPLE 3 Increasing Fabrication Rate: Pressure

A highly oxygen permeable, and UV transparent material is used as thebottom of a chamber filled with photocurable resin in a device of theinvention. During construction, the top of an object is attached to asupport plate which is moved up at a substantially constant speed whilethe bottom portion of the object is constantly being formed just abovethe bottom of the chamber. The gap between the bottom of the object andthe bottom of the chamber is always filled with resin. As the object isbeing formed and advanced, the resin in the gap is constantlyreplenished with supply resin contained in the chamber.

The speed of the object's formation depends on the viscosity of theresin η, atmospheric pressure P, the height of the gap between theobject and the bottom of the chamber h, and the linear dimension L ofthe object's bottom surface. Simple calculations are performed toestimate this speed using the theory of viscous flow between twoparallel plates. The time τ which is required to fill the gap shown onFIG. 7 is given by the equation:

${\left. \tau \right.\sim\left( \frac{L}{h} \right)^{2}}\frac{\eta}{P}$Assuming:

-   -   L˜100 mm    -   h˜100 microns    -   η˜100 cPoise    -   P˜1 atm        In this illustrative embodiment, the time τ is estimated to be        of an order of 1 second, resulting in fabrication speeds of 100        microns per second or 5 minutes per inch. These calculations        assume that the thickness of the uncured resin is maintained at        about 100 microns. Depending on the chemistry of the resin and        permeability of the base plate, this parameter may vary. If, for        example, the gap is 25 microns, then fabrication speeds at        atmospheric pressure will decrease according to Equation 1 by a        factor of 16. However, increasing the ambient pressure to        greater than atmospheric pressure, e.g., by applying external        pressure on the order of 150 PSI as shown in FIG. 8, may in some        embodiments increase fabrication speed by a factor of 10.

When oxygen is the polymerization inhibitor, the gap of uncured resincan be controlled by altering the physical environment in the enclosedchamber contacting feed surface. For example, an atmosphere of pureoxygen, or enriched in oxygen (e.g., 95% oxygen 5% carbon dioxide) canbe provided in place of compressed air, order to increase the gapresulting in increase of fabrication time.

EXAMPLE 4 Fabrication of Rods and Fibers

The methods of the present invention can be used to make an elongate rodor fiber as shown in FIG. 9, the rod or fiber having (for example) awidth or diameter of 0.01 or 0.1 to 10 or 100 millimeters. While acircular cross-section is shown, any suitable cross-section can beutilized, including elliptical, polygonal (triangular, square,pentagonal, hexagonal, etc.) irregular, and combinations thereof. Therod or fiber can have a plurality of elongated pores or channels formedtherein (e.g., 1, 10, 100 1,000, 10,000 or 100,000 or more) of anysuitable diameter (e.g., 0.1 or 1 microns, up to 10 or 100 microns ormore) and any suitable cross-section as described above. Unpolymerizedliquid in the pores or channels can be removed (if desired) by anysuitable technique, such as blowing, pressure, vacuum, heating, dryingand combinations thereof. The length of the rod or fiber can beincreased by utilizing a take-up reel as described above, and the speedof fabrication of the rod or fiber can be increased by carrying out thepolymerization under pressure as described above. A plurality of suchrods or fibers can be constructed concurrently from a single build plateby providing a plurality of independent carriers or take-up reels. Suchrods or fibers can be used for any purpose, such as utilizing each poreor channel therein as an independent channel in a microfluidic system.

EXAMPLE 5 Illustrative Apparatus

An apparatus that can be used to carry out the present invention wasassembled as described above, with a LOCTITE™ UV Curing Wand System asthe ultraviolet light source, a build plate comprised of 0.0025 inchthick Teflon AF 2400 film from Biogeneral clamped in a window andtensioned to substantial rigidity with a tensioning ring, opticalcomponents: from Newport Corporation, Edmund Optics, and Thorlabs, a DLPLightCrafter Development Kit from Texas Instruments as the digitalprojector, a THK Co., LTD ball screw linear stage serving as an elevatorfor the carrier, a continuous servo from Parallax Inc as the elevatorand carrier drive or motor, a motion controller based on a Propellermicrocontroller from Parallax Inc., a position controller based on amagnetic encoder from Austria Microsystems, motion control softwarewritten in SPIN language created by Parallax, open source Slic3r 3Dslicing software, and image control software written using Qt frameworkand Visual C++.

Various different example articles fabricated with this device by themethods described herein are described further below.

EXAMPLE 6 Fabrication of a 700 Micron Microneedle Array

Using an apparatus as described in the example above, trimethylolpropanetriacrylate as the polymerizable liquid, andDiphenyl(2,4,6-trimethylbenzoyl)phosphine oxide as a photoinitiator, thearray of microneedles shown in FIG. 10 was made. The carrier wasadvanced unidirectionally by the ball screw at a continuous rate of 10microns per second and successive exposures were carried out every 2microns along the building height at a duration of 0.2 seconds perexposure. The total number of successive exposures was 350 and the totalfabrication time was 70 seconds.

EXAMPLE 7 Fabrication of a 2000 Micron Microneedle Array

The 2000 micron microneedle array shown in FIG. 11 was made in likemanner as described in example 6 above, with 1000 successive exposuresover a total fabrication time of 200 seconds.

It will be apparent that other arrays, for example with microneedleshaving widths of from 5 to 500 micrometers and heights of 5 to 2000micrometers or more, can be fabricated in like manner. While a squarecross-section is shown, any suitable cross-section can be utilized,including circular, elliptical, polygonal (triangular, rectangular,pentagonal, hexagonal, etc.) irregular, and combinations thereof. Thespacing between microneedles can be varied as desired, for example from5 to 100 micrometers, and the microneedles or other microstructures canbe arranged with respect to one another in any suitable pattern, e.g.,square, rectangular, hexagonal, etc.

EXAMPLE 8 Fabrication of a Ring Structure

A ring was fabricated using the apparatus described in Example 5 above,trimethylolpropane triacrylate as the polymerizable liquid, andDiphenyl(2,4,6-trimethylbenzoyl)phosphine oxide as photoinitiator. Thecarrier was advanced unidirectionally by the ball screw at a continuousrate of 20 microns per second and successive exposures were carriedevery 10 microns along the building height at a duration of 0.5 secondsper exposure. The total number of successive exposures was 1040 and thetotal fabrication time was 520 seconds. FIG. 12 shows the ring duringfabrication, and FIG. 13 shows the ring after fabrication. Note theabsence of supports for extensively overhung elements duringfabrication.

EXAMPLE 9 Fabrication of a Chess Piece

The chess piece shown in FIG. 14 was made using the apparatus describedin the examples above, trimethylolpropane triacrylate as thepolymerizable liquid, and Diphenyl(2,4,6-trimethylbenzoyl)phosphineoxide as photoinitiator. The carrier was advanced unidirectionally bythe ball screw at a continuous rate of 20 microns per second andsuccessive exposures were carried every 10 microns along the buildingheight at a duration of 0.5 seconds per exposure. The total number ofsuccessive exposures was 1070 and the total fabrication time was 535seconds.

EXAMPLE 10 Fabrication of a Ribbed Rectangular Prism

The ribbed rectangular prism shown in FIG. 15 was made using theapparatus described in the Examples above, trimethylolpropanetriacrylate as the polymerizable liquid, andDiphenyl(2,4,6-trimethylbenzoyl)phosphine oxide as the photoinitiator.The carrier was advanced unidirectionally by the worm gear at acontinuous rate of 20 microns per second and successive exposures werecarried every 10 microns along the building height at a duration of 0.5second per exposure. The total number of successive exposures was 800and the total fabrication time was 400 seconds.

EXAMPLE 11 Fabrication of a Coiled or Spiraled Structure

The coil or spiral shown in FIG. 16 was made using the apparatusdescribed in the examples above, trimethylolpropane triacrylate as thepolymerizable liquid, and Diphenyl(2,4,6-trimethylbenzoyl)phosphineoxide as the photoinitiator. The carrier was advanced unidirectionallyby the ball screw at a continuous rate of 20 microns per second andsuccessive exposures were carried every 10 microns along building heightat a duration of 0.5 seconds per exposure. The total number ofsuccessive exposures was 970 and the total fabrication time was 485seconds.

Note that this extensively cantilevered structure was fabricated free ofany supporting structures.

EXAMPLE 12 Curing Depth vs. Exposure Time

An experiment was performed with various concentrations of amber candledye and photo initiator (PI) in trimethylolpropane triacrylate as thepolymerizable liquid and Diphenyl(2,4,6-trimethylbenzoyl)phosphine oxideas photoinitiator. Results are shown in FIG. 17. The image used was a 6mm circle, which produced a disk-like part in the resin bath, whencured. The thickness of the disk varied based on the exposure time andthe concentration of photo initiator and dye in the resin. All resinmixtures would begin curing quickly and approach a limiting value. Theoptimal resin should cure in a short period of time and the limitingvalue should be as small as possible. The two resins that best fit thosecriteria are the 3% photo initiator with 0.05% dye (fine dots) and 5%photoinitiator with no dye (solid). These resins also produce the bestprinted parts in terms of feature contrast and clarity.

A chess piece made with such a dye-containing resin is shown in FIG. 18.

EXAMPLE 13 Carrier Soluble Sacrificial (or Release) Layers

A deficiency of prior techniques is that the requirement to “break”adhesion from the build plate, e.g., by sliding the build plate, or byusing an elastic build plate, made it problematic to employ a releaselayer or soluble adhesive layer on the carrier that might prematurelyfail during the fabrication process. The present invention facilitatesthe employment of a release layer on the carrier during fabrication.

The surface of the carrier can be coated with a release layer, i.e., asoluble sacrificial layer (e.g., cyanoacrylate adhesive), and array ofobjects can be printed as shown in FIG. 19. Any suitable thickness ofrelease layer can be used, for example from 100 nanometers to 1millimeter. Submerging the carrier with the fabricated objects into anappropriate solvent (e.g., acetone for cyanoacrylate adhesive) thatselectively dissolves or solubilizes the release layer then releases theobjects from the carrier as shown in FIG. 20.

EXAMPLE 14 Fabricating Rectangular Prisms on a Release Layer

The array of rectangular prisms with dimensions of 200×200×1000micrometers shown in FIG. 21 was made using the apparatus describedabove, trimethylolpropane triacrylate as the polymerizable liquid,diphenyl(2,4,6-trimethylbenzoyl)phosphine oxide as the photoinitiator,and cyanoacrylate adhesive as release layer. The carrier was advanced bythe ball screw at a continuous rate of 10 microns per second andsuccessive exposures were carried every 10 microns along the buildingheight at a duration of 1 second per exposure. The total number ofsuccessive exposures was 100 and the total fabrication time was 100seconds. The cyanoacrylate release layer was then dissolved by acetoneto produce free floating prisms as shown in FIG. 22.

EXAMPLE 15 Fabrication of Cylindrical Cage Structures

The cylindrical cage structure of FIG. 23 was made using the apparatusdescribed in the Example above, trimethylolpropane triacrylate as thepolymerizable liquid, and diphenyl(2,4,6-trimethylbenzoyl)phosphineoxide as photoinitiator. The carrier was advanced by the ball screw at acontinuous rate of 20 microns per second and successive exposures werecarried out every 10 micron along the building height at a duration of0.5 seconds per exposure. The total number of successive exposures was1400 and the total fabrication time was 700 seconds. No removablesupporting structures for cantilevered features or “overhangs” wereused.

EXAMPLE 16 Fabrication of Structures from a Hydrogel

FIG. 24 and FIG. 25 are photographs of array structures and cagestructures, respectively, produced in like manner as those describedabove, except that they were fabricated using PEG (Poly(ethylene glycol)diacrylate, average Mn 700) as the polymerizable liquid and 5% ofDiphenyl(2,4,6-trimethylbenzoyl)phosphine oxide as the photoinitiator.Processing conditions were otherwise the same as for the previouslyfabricated triacrylate parts.

EXAMPLE 17 Flexibility of Hydrogel Based Parts

The cylindrical cage structure produced in Example 23 above and shown inFIG. 25 was manually positioned between two glass microscope slides andpressure manually applied until the cylindrical cage structure wasdeformed and substantially flat. Manual pressure was then released, andthe cage structure returned to its previous substantially cylindricalform. The flexibility, resiliency, and shape memory properties of thearticles make them attractive for a variety of uses, including but notlimited to stents for various biomedical applications.

EXAMPLE 18 Fabrication of Intraluminal Stents for Therapeutic Use

Stents are typically used as adjuncts to percutaneous transluminalballoon angioplasty procedures, in the treatment of occluded orpartially occluded arteries and other blood vessels. As an example of aballoon angioplasty procedure, a guiding catheter or sheath ispercutaneously introduced into the cardiovascular system of a patientthrough a femoral artery and advanced through the vasculature until thedistal end of the guiding catheter is positioned at a point proximal tothe lesion site. A guidewire and a dilatation catheter having a balloonon the distal end are introduced through the guiding catheter with theguidewire sliding within the dilatation catheter. The guidewire is firstadvanced out of the guiding catheter into the patient's vasculature andis directed across the vascular lesion. The dilatation catheter issubsequently advanced over the previously advanced guidewire until thedilatation balloon is properly positioned across the vascular lesion.Once in position across the lesion, the expandable balloon is inflatedto a predetermined size with a radiopaque liquid at relatively highpressure to radially compress the atherosclerotic plaque of the lesionagainst the inside of the artery wall and thereby dilate the lumen ofthe artery. The balloon is then deflated to a small profile so that thedilatation catheter can be withdrawn from the patient's vasculature andblood flow resumed through the dilated artery.

Balloon angioplasty sometimes results in short or long term failure.That is, vessels may abruptly close shortly after the procedure orrestenosis may occur gradually over a period of months thereafter. Tocounter restenosis following angioplasty, implantable intraluminalprostheses, commonly referred to as stents, are used to achieve longterm vessel patency. A stent functions as scaffolding to structurallysupport the vessel wall and thereby maintain luminal patency, and aretransported to a lesion site by means of a delivery catheter.

Types of stents may include balloon expandable stents, spring-like,self-expandable stents, and thermally expandable stents. Balloonexpandable stents are delivered by a dilation catheter and areplastically deformed by an expandable member, such as an inflationballoon, from a small initial diameter to a larger expanded diameter.Self-expanding stents are formed as spring elements which are radiallycompressible about a delivery catheter. A compressed self-expandingstent is typically held in the compressed state by a delivery sheath.Upon delivery to a lesion site, the delivery sheath is retractedallowing the stent to expand. Thermally expandable stents are formedfrom shape memory alloys which have the ability to expand from a smallinitial diameter to a second larger diameter upon the application ofheat to the alloy.

It may be desirable to provide localized pharmacological treatment of avessel at the site being supported by a stent. Thus, sometimes it isdesirable to utilize a stent both as a support for a lumen wall as wellas a delivery vehicle for one or more pharmacological agents.Unfortunately, the bare metallic materials typically employed inconventional stents are not generally capable of carrying and releasingpharmacological agents. Previously devised solutions to this dilemmahave been to join drug-carrying polymers to metallic stents.Additionally, methods have been disclosed wherein the metallic structureof a stent has been formed or treated so as to create a porous surfacethat enhances the ability to retain applied pharmacological agents.However, these methods have generally failed to provide a quick, easyand inexpensive way of loading drugs onto intraluminal prostheses, suchas stents. In addition, only small amounts of drugs can be loaded intothin polymeric coatings.

Intraluminal prostheses, such as stents have been developed usingvarious polymeric materials and/or coatings of polymeric materials toovercome the limitations of conventional metallic prostheses. However,it would be desirable to be able to adjust various mechanical properties(e.g., modulus, hoop strength, flexibility, etc.) of polymericintraluminal prostheses. For example, for intraluminal prostheses usedto deliver pharmacological agents, it would be desirable to be able toadjust the elution rate of a pharmacological agent therefrom. As anotherexample, it would be desirable to be able to adjust the degradation rateand/or the nature of degradation of the polymeric material.

According to embodiments of the present example, methods ofmanufacturing polymeric intraluminal prostheses (e.g., formed frompolymeric material to include suitably functionalized PEG, PLGA,polycaprolactone, gelatin, etc) include annealing the polymeric materialto selectively modify the crystallinity or crystalline structure thereofis accomplished by the methods described herein, including but notlimited to those set forth in connection with cylindrical cagestructures as described above.

Pharmacological agents disposed on or within the polymeric material mayinclude, but are not limited to, agents selected from the followingcategories: antineoplastics, antimitotics, antiinflammatories,antiplatelets, anticoagulants, antifibrins, antithrombins,antiproliferatives, antibiotics, antioxidants, immunosuppressives,antiallergic substances, and combinations thereof.

According to other embodiments of the present invention, the degree ofmolecular crosslinking of the polymeric material of an intraluminalprostheses may be modified by subjecting the polymeric material tochemical treatment and/or irradiation. The polymeric material may besubjected to chemical treatment and/or irradiation before, during and/orafter annealing. Such treatments may also act as a sterilization step.

EXAMPLE 19 Fabrication of Therapeutic Microneedle Arrays

Many promising new therapeutics are large biomolecules, such aspeptides, proteins, antibodies, and nucleic acids. These molecules canbe too large, fragile, or insoluble for delivery by traditional routesof introduction. Hypodermic injection (including intravascular,intramuscular, etc.) enables the delivery of sensitive therapeutics, butthey induce pain, provide opportunities for accidental needle sticks,and produce sharp, biohazardous waste. Furthermore, in the case ofvaccine delivery, hypodermic needles do not deliver doses to the optimumlocation to elicit an immune response; they penetrate into muscle, aregion known to have a lower density of immunologically sensitive cellsthan skin. Transdermal patches are effective for select time-releaseddrugs (like nicotine and motion sickness medications), but the epidermis(specifically the stratum corneum) limits the diffusion of most drugs(>500 Da) through the skin. Clearly, the ability to transporttherapeutics effectively into the body remains a significant challenge.

While there are limitations to traditional transdermal drug delivery,which typically relies on the passive diffusion of therapeutics throughthe skin, this route of administration remains very promising.

Using the apparatus described in the Examples above andphotopolymerizable, biocompatible and biodegradable resins (suitablyfunctionalized PEG, PLGA, polycaprolactone, gelatin, etc) are used incombination with therapeutics and vaccine elements (antigens, adjuvants,etc), to produce therapeutic microneedle arrays having essentially thesame structure or appearance as those shown above. Those skilled in theart will appreciate numerous different structures and architectures forsuch therapeutic microneedle arrays which can be produced by the methodsand apparatus described herein.

EXAMPLE 20 Dependence of Vertical Resolution on Fabrication Speed

During the part build process the controller image processing unit (IPU)in some embodiments is constantly updating images of cross sectionallayers of the part. The maximum speed of image update f can in someembodiments vary from 1 frame per second up to 1000 frames per second,depending on the hardware.

If the desired vertical resolution is delta then during the buildprocess the advancement dz of the part carrier during one image frameshould be less than delta. If the fabrication speed is ν then dz isgiven by

${dz} = \frac{v}{f}$

In order to achieve resolution delta, fabrication speed ν should be lessthan the maximum fabrication speed ν_(max) given byν_(max) =Δf

Two chess piece parts similar to those illustrated above were made acarrier advancement speed of 250 mm/hour and 500 mm/hour. The maximumframe rate of the particular IPU used to make the parts wasapproximately 1 frame per second. The estimated resolution of theseparts was 50 micrometers at 250 mm/hour, and 100 micrometer at 500mm/hour.

EXAMPLE 21 Increasing Fabrication Rate: Temperature

Increasing fabrication rate by pressure is described above. In addition,in the methods and apparatus set forth both generally and specificallyabove and below, fabrication rate can be increased by heating thepolymerizable liquid, or resin, to reduce the viscosity thereof, tofacilitate filling of the build zone with the polymerizable liquid ormigration of the polymerizable liquid into the build zone (with orwithout increased pressure). Some resins, such as high performanceresins including those noted above, may be solid at room temperature andpressure, and heating may be a convenient way to liquefy the same.

Heating may be carried out by any suitable technique, such as withclosed-oven infrared heaters operatively associated with a temperaturesensor and controller, as schematically illustrated in FIG. 26. Numerousadditional types and configurations of heaters may be used, alone or incombination with the foregoing and one another. Resistive heaters may beused, for example submersed in the polymerizable liquid on the buildplate. Thermoelectric devices or Peltier heaters can be used, forexample contacting the build plate and/or the polymerizable liquid. Thepolymerizable liquid can be pre-heated, in a storage reservoir and/orthrough various feed lines. One or more temperature sensors can beemployed to detect ambient (in chamber) temperature, build platetemperature, carrier temperature, polymerizable liquid temperature(e.g., at any point, such as on the build plate), etc.

In some embodiments, the polymerizable liquid is heated by at least 5,10, 20, 40, 60, 80, or 100 degrees Centigrade or more above roomtemperature.

In some embodiments, the polymerizable liquid has a viscosity of atleast 100, 1,000, or 10,000 centipoise, up to 1,000,000 centipoise ormore at 25 degrees Centigrade and atmospheric pressure (note 1centipoise=1 milliPascal seconds). In some embodiments, suchpolymerizable liquids can have a viscosity when heated (e.g., by theamount described above) of not more than 1,000, 100, 10 or 1 centipoise.Specific end viscosity desired to be achieved will depend on factorssuch as the rate of fabrication desired, size and shape of the articlebeing fabricated, the presence or absence of increased pressure, etc.

Viscosity can be measured by any suitable technique, for example by aBrookfield viscometer having a cone and plate geometry, with a coneangle of 1 degree, a 40 millimeter diameter, operated at 60 revolutionsper minute.

Coolers can optionally be included if desired to more rapidly correcttemperature (with heaters, or without heaters, e.g., to aid indissipating heat generated exothermically by rapid photopolymerization.Again, any suitable cooler configuration can be used, generallyoperatively associated with a controller and temperature sensor as notedabove. Heat exchangers, heat sinks, refrigerants, thermoelectric devicessuch as Peltier coolers (which may also serve as Peltier heaters), etc.may be employed.

EXAMPLE 22 Feeding Resin Through the Carrier and Internal Feed Channels

As discussed in Example 3 the speed of the object's formation depends onthe linear dimension L of the object's bottom surface, viscosity of theresin η, atmospheric pressure P, and the height of the gap between theobject and the bottom of the chamber h. The time τ which is required tofill the gap between the object and the bottom of the chamber is:

${\left. \tau \right.\sim\left( \frac{L}{h} \right)^{2}}\frac{\eta}{P}$As one can see 10 fold increase in the part size results in 100 folddecrease in fabrication speed. To eliminate such strong dependence offabrication speed on part size, polymerizable liquid (or resin) can befed through the part carrier and through the part as shown in FIG. 27.

The pump can comprise any suitable pumping device, including but notlimited to syringe pumps, gear pumps, peristaltic pumps, etc. The rateat which pump operates is controlled by a controller and depends on partgeometry and speed of fabrication

In this approach dependence of part fabrication rate on linear dimensionL of the object's bottom surface, viscosity of the resin η, atmosphericpressure P, and the height of the gap between the object and the bottomof the chamber h is no longer limited by above equation but it is rathercontrolled by the rate at which resin pump operates, the rate of thecuring reaction and the ability to mitigate heat removal from the curingreaction. The pump in this example could comprise a syringe pump, gearpump, or peristaltic pump. The pump operation could be included intofeedback loop controlled by central processing unit where pumping ratesdepend on part geometry and desired fabrication speed.

EXAMPLE 23 Resin Feed Rate Control: Feed-Forward Control

During the part build process the resin consumption rate changes basedon the cross sectional area of the part. A process to control resindelivery rate is described below. If the build speed is ν and the crosssection of the part A varies with time t as A (t) then resin deliveryrate can be adjusted to correspond, in whole or in part, to:R(t)=vA(t)For example, during the build process a central processing unit (CPU)serving as a controller can in real time calculate the current crosssection of the part, then calculate delivery rate based on a rule suchas the equation above and communicate the calculated rate to a resindelivery pump controller (RDPC). The RDPC can then adjust the speed ofthe resin delivery pump based on the data received from CPU.

Such a feed-forward control system can be used alone or in combinationwith other feed forward and feed-back control systems (e.g., temperatureand/or pressure control) as described above.

EXAMPLE 24 Feeding Polymerizable Liquid Through External Feed Conduits

In some embodiments where polymerizable liquid is supplied through oneor more channels formed in the carrier, it may be desired that some, orall, of the article being fabricated be solid throughout. In such cases,separate or external feed conduits in fluid communication with a (oreach) channel supplying polymerizable liquid may be concurrentlyfabricated adjacent the article being fabricated (In contrast to one ormore internal feed channels formed within the article being produced.

The polymerizable liquid can then be provided through the external feedconduit(s) to the build plate and fabrication zone. In some embodimentsmultiple such feed conduits may be constructed, e.g., 2, 10, 100, or1000 or more, depending on the size of the article being fabricated.Such external feed conduits may be used in combination, concurrently orsequentially (e.g., alternatively), with internal feed channels (i.e.,channels formed within the article being fabricated).

EXAMPLE 25 Fabrication with Multiple Distinct Resins with Multiple FeedConduits

Articles can be fabricated using multiple resins by feeding thedifferent resins through the build platform, and using them to createtubes or channels to deliver the resin to the correct area of the partbeing fabricated.

FIG. 28 illustrates the method that can be used to feed resin throughthe build platform, use it to fabricate the resin delivery channels inthe necessary shape, and when necessary, feed extra resin to fabricatethe part itself. When the section has finished fabrication, the channelis cured shut and another channel can begin feeding the next resin tocontinue fabricating the part.

EXAMPLE 26 Control of Method and Apparatus

A method and apparatus as described above may be controlled by asoftware program running in a general purpose computer with suitableinterface hardware between that computer and the apparatus describedabove. Numerous alternatives are commercially available. Non-limitingexamples of one combination of components is shown in FIGS. 29-31, where“Microcontroller” is Parallax Propeller, the Stepper Motor Driver isSparkfun EasyDriver, the LED Driver is a Luxeon Single LED Driver, theUSB to Serial is a Parallax USB to Serial converter, and the DLP Systemis a Texas Instruments LightCrafter system.

The foregoing is illustrative of the present invention, and is not to beconstrued as limiting thereof. The invention is defined by the followingclaims, with equivalents of the claims to be included therein.

That which is claimed is:
 1. A method of forming a three-dimensionalobject, comprising the steps of: (a) providing a carrier and a buildplate, said build plate comprising a semipermeable member, saidsemipermeable member comprising a build surface, with said build surfaceand said carrier defining a build region therebetween, and with saidbuild surface in fluid communication by way of the semipermeable memberwith a source of polymerization inhibitor; (b) filling said build regionwith a polymerizable liquid, said polymerizable liquid contacting saidbuild surface; (c) irradiating said build region through said buildplate to produce a solid polymerized region in said build region, whileforming or maintaining a liquid film release layer comprised of saidpolymerizable liquid between said solid polymerized region and saidbuild surface, the polymerization of which liquid film is inhibited bysaid polymerization inhibitor; and (d) advancing said carrier with saidpolymerized region adhered thereto away from said build surface on saidbuild plate to create a subsequent build region between said polymerizedregion and said build surface; (e) continuing and/or repeating steps (b)through (e) to produce a subsequent polymerized region adhered to aprevious polymerized region until the continued or repeated depositionof polymerized regions adhered to one another forms saidthree-dimensional object; (f) wherein said carrier has at least onechannel formed therein, and said filling step is carried out by passingor forcing said polymerizable liquid into said build region through saidat least one channel and through said object.
 2. The method of claim 1,wherein said carrier has a plurality of channels formed therein, andwherein different polymerizable liquids are forced through differentones of said plurality of channels.
 3. The method of claim 1, furthercomprising concurrently forming at least one, or a plurality of,external feed conduits separate from said object, each of said at leastone feed conduits in fluid communication with a channel in said carrier,to supply at least one, or a plurality of different, polymerizableliquids from said carrier to said build region.
 4. A method of forming athree-dimensional object, comprising the steps of: (a) providing acarrier and a build plate, said build plate comprising a semipermeablemember, said semipermeable member comprising a build surface, with saidbuild surface and said carrier defining a build region therebetween, andwith said build surface in fluid communication by way of thesemipermeable member with a source of polymerization inhibitor; (b)filling said build region with a polymerizable liquid, saidpolymerizable liquid contacting said build surface; (c) irradiating saidbuild region through said build plate to produce a solid polymerizedregion in said build region, while forming or maintaining a liquid filmrelease layer comprised of said polymerizable liquid between said solidpolymerized region and said build surface, the polymerization of whichliquid film is inhibited by said polymerization inhibitor; and (d)advancing said carrier with said polymerized region adhered thereto awayfrom said build surface on said build plate to create a subsequent buildregion between said polymerized region and said build surface; (e)continuing and/or repeating steps (b) through (e) to produce asubsequent polymerized region adhered to a previous polymerized regionuntil the continued or repeated deposition of polymerized regionsadhered to one another forms said three-dimensional object; (f) whereinsaid carrier has at least one channel formed therein, and said fillingstep is carried out by passing or forcing said polymerizable liquid intosaid build region through said at least one channel and through saidobject; wherein steps (b) through (e) are carried out concurrently. 5.The method of claim 1, wherein the build plate is stationary.
 6. Themethod of claim 1, wherein the source of polymerization inhibitor is areservoir of polymerization inhibitor within the semipermeable member.7. The method of claim 1, wherein the semipermeable member furthercomprises a feed surface separate from said build surface.
 8. The methodof claim 7, wherein the feed surface is in fluid contact with apolymerization inhibitor so as to provide said source of polymerizationinhibitor.
 9. The method of claim 1, wherein said advancing step orsteps is/are carried out at a cumulative rate of at least 10 microns persecond.
 10. The method of claim 1, wherein excess polymerizable liquidis supplied to said build region, removed or drained therefrom to coolsaid build region, and then optionally recirculated back to said buildregion.
 11. The method of claim 1, wherein said advancing step iscarried out by advancing said carrier vertically from said buildsurface.
 12. The method of claim 7, wherein: said semipermeable membercomprises a top surface portion, a bottom surface portion, and an edgesurface portion; said build surface is on said top surface portion; andsaid feed surface is on at least one of said top surface portion, saidbottom surface portion, and said edge surface portion.
 13. The method ofclaim 1, wherein said irradiating step is carried out with actinicradiation.
 14. The method of claim 1, wherein: a total surface area ofthe build region occupies at least seventy percent of a total surfacearea of the build surface; and/or wherein lateral movement of thecarrier and object in any direction is not more than thirty percent of awidth of said build region in the corresponding direction.
 15. Themethod of claim 1, wherein (a) said polymerizable liquid comprises afree radical polymerizable liquid and said inhibitor comprises oxygen,or (b) said polymerizable liquid comprises an acid-catalyzed orcationically polymerizable liquid, and said inhibitor comprises a base.16. The method of claim 1, wherein said polymerizable liquid furthercomprises an active agent, a detectable agent, solid particles, or acombination thereof.
 17. The method of claim 1, wherein said irradiatingstep is carried out by maskless photolithography.
 18. A method offorming a three-dimensional object, comprising the steps of: (a)providing a carrier and a build plate, said build plate comprising asemipermeable member, said semipermeable member comprising a buildsurface, with said build surface and said carrier defining a buildregion therebetween, and with said build surface in fluid communicationby way of the semipermeable member with a source of polymerizationinhibitor; (b) filling said build region with a polymerizable liquid,said polymerizable liquid contacting said build surface; (c) irradiatingsaid build region through said build plate to produce a solidpolymerized region in said build region, while forming or maintaining aliquid film release layer comprised of said polymerizable liquid betweensaid solid polymerized region and said build surface, the polymerizationof which liquid film is inhibited by said polymerization inhibitor; and(d) advancing said carrier with said polymerized region adhered theretoaway from said build surface on said build plate to create a subsequentbuild region between said polymerized region and said build surface; (e)wherein said carrier has at least one channel formed therein, and saidfilling step is carried out by passing or forcing said polymerizableliquid into said build region through said at least one channel; furthercomprising the steps of: monitoring or detecting at least one processparameter and/or providing at least one known or predetermined processparameter; and then altering at least one process condition in responseto said monitored process parameter or known process parameter.
 19. Themethod of claim 1, wherein the carrier with said polymerized regionadhered thereto is unidirectionally advanced away from said buildsurface on said stationary build plate.
 20. A method of forming athree-dimensional object, comprising the steps of: (a) providing acarrier and a build plate, said build plate comprising a semipermeablemember, said semipermeable member comprising a build surface with saidbuild surface and said carrier defining a build region therebetween, andwith said build surface in fluid communication by way of thesemipermeable member with a source of polymerization inhibitor; (b)filling said build region with a polymerizable liquid, saidpolymerizable liquid contacting said build surface; (c) irradiating saidbuild region through said build plate to produce a solid polymerizedregion in said build region, while forming or maintaining a liquid filmrelease layer comprised of said polymerizable liquid between said solidpolymerized region and said build surface, the polymerization of whichliquid film is inhibited by said polymerization inhibitor; and (d)advancing said carrier with said polymerized region adhered thereto awayfrom said build surface on said build plate to create a subsequent buildregion between said polymerized region and said build surface; (e)wherein said carrier has at least one channel formed therein, and saidfilling step is carried out by passing or forcing said polymerizableliquid into said build region through said at least one channel; and (f)wherein said advancing step is carried out while also concurrently (i)continuously maintaining a dead zone of polymerizable liquid in contactwith said build surface, and (ii) continuously maintaining a gradient ofpolymerization zone between said dead zone and said solid polymer and incontact with each thereof, said gradient of polymerization zonecomprising said polymerizable liquid in partially cured form.
 21. Themethod of claim 5, wherein said semipermeable member comprises aflexible polymer film, and said build plate further comprises atensioning member connected to said polymer film to fix and rigidify thefilm.
 22. The method of claim 21, wherein said flexible polymer filmcomprises a fluoropolymer film.
 23. The method of claim 20, wherein saidbuild plate is stationary.
 24. The method of claim 23, wherein saidsemipermeable member comprises a flexible polymer film, and said buildplate further comprises a tensioning member connected to said polymerfilm to fix and rigidify the film.
 25. The method of claim 18, wherein:said process parameter is expected consumption of polymerizable liquid;and said process condition is a rate of supply of polymerizable liquid.26. The method of claim 1, wherein said semipermeable member comprises afluoropolymer film.
 27. The method of claim 4, wherein saidsemipermeable member comprises a fluoropolymer film.
 28. The method ofclaim 18, wherein said semipermeable member comprises a fluoropolymerfilm.
 29. The method of claim 20, wherein said semipermeable membercomprises a fluoropolymer film.
 30. The method of claim 18, wherein saidprocess condition is rate of supply of polymerizable liquid,temperature, pressure, rate or speed of advance of carrier, intensity ofirradiation, or duration of irradiation.